Dose standardisation of intravenous anticancer drugs: Risk analysis and implementation in a French cancer centre

Abstract

Objective

Implementation of a Standard Doses (SD) workflow is a big challenge for pharmacists, in order to optimize the organization of chemotherapy preparation and support in day hospital activity. The objective is to map and determine the feasibility of a SD routine and to identify eligible molecules with and corresponding SD.

Methods

A Preliminary Risk Analysis (PRA) of the process from prescription to preparation was carried out, with a failure mode and effects critical analysis (FMECA) method. A survey on standard dose concept was distributed to all prescribers. The rules to define eligible dosage of each drugs was an annual production of more than 250 preparations and for each eligible molecule, at least a 70% coverage rate for a maximum of 7 SD. These doses have been rounded up to a maximum of +/- 10% for cytotoxics and antibody-drug conjugates, and +/- 15% for monoclonal antibodies.

Results

After medical approval, sixteen molecules were eligible and thirteen are used routinely to date. The PRA highlighted 52 risks over 16 stages of the process. A risk retains a significant criticality after application of control actions: the risk of musculoskeletal disorders (MSD) during preparation.

Conclusion

This work enabled us to study the feasibility of setting up a SD workflow in our hospital to optimize the provision of chemotherapy to the patient. Due to persistent MSD risk and limited storage capacity, we decided to prescribe exclusively in SD, pending the automation of our preparation unit in 2025.

Keywords

Dose banding anticancer drugs risk analysis

Introduction

Cancer is a leading global cause of death, with nearly 10 million deaths in 2020, or one in six deaths.^1,2 Over the decades, significant progress has been made in improving patient care thanks to early diagnosis and a growing therapeutic arsenal.^3,4 This leads to an increasing number of patients requiring hospitalization, especially for intravenous anticancer drugs, predominantly administered in day hospitals. (e.g., 92% during 2020 in France).⁴

Day hospitals offer many benefits, both for patient and healthcare establishment. Indeed, they reduce the time of presence in the hospital, allowing cost saving, and optimized patient throughput.⁴ However, one of the main problems of day hospitals is the waiting time between appointment time of patient and beginning of treatment. And this waiting time has a real impact on patient the experience and satisfaction^5,6 which is essential for acceptance and adherence to treatment.

Moreover, the workload generated by the rotation of patients in day hospital is concentrated over a short period. This results in a fluctuation in activity with daily peaks that can increase the delays in dispensing chemotherapy by hospital pharmacies. These peaks are also a source of stress, both for pharmaceutical and nursing staff, which can lead to preventable adverse events associated with care, such as medication errors.

In response to these issues, several solutions have been adopted by healthcare establishments in order to streamline activity and optimize delivery times for injectable cancer drugs: –

Early medical validation of chemotherapy, using up to date information, such as the last biological parameters, collected from computerized medical files and a phone call to the patient is made whenever deemed necessary

–

Advance preparation before medical validation, necessitating a reallocation system to limit waste and additional costs

–

Optimize patient's care pathways (use of a software to schedule the patient's medical appointments, implementation of Lean management concept,…)⁷

–

Purchase of industrial bags with standardized doses (e.g., Gemcitabine from the SUN laboratory)

–

Dose Banding (DB) concept, or dose standardization.⁸

The delivery of medication by the pharmacy to the day-hospital care unit occurs only after medical approval. The concept of DB originated in the UK in the late 1990s. Since then, it has been widely used in the UK for the preparation of chemotherapy for both inpatients and outpatients.⁹

In DB, doses of IV anticancer drugs are calculated individually according to the Body Surface Area (BSA). Then, after agreement between prescribers and pharmacists, these doses are adjusted to dose intervals or "bands." The midpoint of each band is a predetermined Standard Dose (SD). The maximum variation in adjustment, between the SD and the BSA-calculated doses, is usually set arbitrarily at 5%. The goal of the DB is to systematize the rounding practice based on clinical and product strength, so that only one dose is proposed per defined BSA interval. This is intended to improve the logistics of making chemotherapy available.^2,8^10–12 In practice, higher roundings may be used: for example, HOPA recommends a rounding of 10% for anti-cancer drugs, or even more for monoclonal antibodies (per vial for some). In fact, the difference linked to the DB is much smaller than the 20 to 30% adjustments applied to improve tolerance or therapeutic response. Furthermore, despite the dosage prescribed according to the BSA, effect of a 10% dose rounding on AUC will generally be eclipsed by the degree of interindividual pharmacokinetic variability that will determine systemic drug exposure. In the case of monoclonal antibodies, the therapeutic range, as well as the often higher cost and shorter shelf life, are further arguments in favour of dose standardisation.¹³

Another point is that the injectable anticancer drug circuit is complex, because it consists of a large number of steps and involves multiple stakeholders. This circuit is subject to various constraints: control of chemical and microbiological risks, centralization of drug preparation, physico-chemical stability of preparations.^2,14 Anticancer drugs are a pharmaceutical class which requires particular vigilance because of the risk it generates, both for patients and for nursing staff during the process of its use.²^15–17 Hence the emergence of quality requirements related to the preparation of injectable chemotherapies as well as risk control. At the time this work was conducted (2020–2021), international consensus documents on dose banding were still limited. Since then, the “ISOPP Standards for the Safe Handling of Cytotoxics” has been published in 2022, providing a comprehensive framework and an update to the 2007 standards, in line with developments in oncology pharmacy practices.² In France, there is the example of “Good Preparation Practices” guide, the 2022 version of which stresses the importance of carrying out a risk analysis when carrying out risky pharmacotechnical activities, such as the preparation of injectable anticancer drugs.¹⁸

Thus, the aim of this work was to set up a Standard Dose (SD) circuit at Curie Institute, at Saint-Cloud (Hauts-de-Seine, France), with determination of eligible anticancer drugs, standardized doses and intervals, in order to optimize the general circuit of injectable anticancer drugs. A risk analysis was also carried out to determine the feasibility of the project and to secure its implementation.

Methods

Risk analysis

An a priori risk assessment was carried out by a multidisciplinary working group, according to a methodology recommended by the French Health Authority (HAS).¹⁹ This working group is made up several pharmacists and a pharmacy resident, to model Standard Doses circuit and build the tool. We chose the Failure Mode, Effects and Criticality Analysis (FMECA) method. Indeed, this one has already been used in our hospital to assess the patient's drug management, or to analyse the impact of anticipation of injectable anticancer drugs prescription. In order to improve the identification, the rating of the identified risks and the control actions of risk, we had support from technician health manager and the quality manager of the establishment's Quality-Risk Management department.

The approach began with construction of the future SD circuit, with a description of each process, from determination of SD of chemotherapies to their administration. General anticancer drugs circuit were analysed, as well as the first SD circuit implanted in the other site (Paris Curie Institute). SD concept was integrated into the existing process at Saint-Cloud using Microsoft Visio^®, software for creating diagrams and synoptics. Each step of the process, as well as each stakeholder, has been represented.

Potential failure modes have been identified, and ranked according to Frequency (F) of occurrence, Severity (S) and Initial Criticality (Ci). F and S were determined with a 5-level scale. Ci corresponds to the product of F and S, and is quoted with a 3-level scale. Control actions have been considered based on the score obtained and a risk control level (M) is determined with a 5-level scale. The product of Ci and M corresponds to the Residual Criticality (Cr), ranked with a 3-level scale, used to assess the feasibility of the project. All these elements are summarized in table 1.

Table 1.

Risk assessment scales and criteria.

Scale	Level	Description
Frequency of occurrence (F)	1. Very rare	The cause never happened or only happened once in several years
	2. Rare	At least once a year
	3. Occasional	At least once a month
	4. Frequent	At least once a week
	5. Very frequent / usual	At least once a day
Consequences severity (S)	1. Minor	Minor consequences without prejudice Ex: Simple delay: delivery or performance of service without consequence Minor defect not affecting the quality of the product or its use
	2. Significant	Incident with temporary damage Ex: Delay with disorganized treatment Delay in delivery or performance of a service with consequences Occasional deterioration in the quality of the product / service
	3. Major	Incident with impact Ex: Postponement or abnormal extension of hospitalization Transient loss of function Temporary stoppage (short term) of the production of the product or a service Persistent deterioration in the quality of the product / service
	4. Critical	Serious consequences Ex: Re-intervention, Permanent partial incapacity Prolonged stoppage of the production of the product/service
	5. Catastrophic	Very serious consequences Ex: Permanent disability, serious sequelae, death Biological result error Unrealized / unrealizable service
Risk control (M)	1. Very good	We know how to deal with, good control: plans with exercises and training, monitoring, control, continuous improvement
	2. Good	We have everything planned: action plans in place with indicators
	3. Average	We organized: organization in place without evaluation
	4. Weak	We are on the alert: some actions but insufficient – watch but without actions
	5. Bad / Nonexistent	We discover the risk: no action in place – studies in progress – actions inefficient
Initial Criticality (Ci)	1 to 4	Low risk
	5 to 10	Moderate risk
	12 to 25	Major risk
Residual Criticality (Cr)	1 to 9	Acceptable risk
	10 to 32	Risk to watch
	36 to 125	Risk to be treated

Dose standardization of anticancer drugs

Concerning dose standardization, the theoretical SD have been pre-determined on basis of the most frequently prescribed dosages of anticancer drugs corresponding to protocols and to the indications of the Summary of Product Characteristics (SPC). We extracted production data for the year 2020 from the CHIMIO^® software. Our selection criteria were: –

Minimum production threshold of 250 preparations per year

–

Percentage of coverage of the annual production of anticancer drug greater than 70% with a maximum of 7 SD: i.e., 7 SDs max are needed to cover 70% of the annual production of the selected INN

–

Maximum tolerated deviation from the initial prescription was 10% for cytotoxics and Antibody Drug Conjugates (ADC), and 15% for Monoclonal Antibody (MAB).

Whenever possible, SD were rounded to the vial or to multiples of vials or, failing that, to the syringe pitch, to facilitate preparation. In parallel, we built and distributed an online questionnaire (available table 2) to prescribers in the institution to introduce and assess their knowledge of the concept.

Table 2.

Questionnaire on anticancer prescribing practices and dose standardisation.

Section 1: current prescribing practices

1a: Do you apply additional dose rounding when prescribing?

□ Yes

□ No

1b: If yes, how?

□ Rounding to a whole number (unit, ten, hundred…),

□ Percentage of rounding

□ Other, specify: __________

1c: If yes, on which molecules?

□ Cytotoxics

□ Monoclonal antibodies

□ Antibody drug conjugate

1d: If no, specify: __________

Section 2: awareness of dose banding concept

2. Are you aware of the concept of Dose Banding or dose standardization?

□ Yes

□ No

Section 3: perception and acceptance of the concept

3.a Would you approve of the implementation of this concept when prescribing?

□ Yes

□ No

3.b What would be for you the maximum percentage of difference with the initial prescription?

□ Open response: __________%

4. What do you see as the benefits of this type of concept?

□ Open response: __________

Section 4: suggestion and comments

5: Do you have any suggestions/comments to optimize the prescribing and/or the chemotherapy circuit?

□ Open response: __________

Results

Risk analysis

Firstly, the process mapping made it possible to identify a 16-step process (detailed table 3 ): including all the upstream steps, like determination of the SD for example. Then, the steps in the chemotherapy circuit, with prescription, validation, preparation, etc. Finally, this process of setting up the SD also includes additional steps such as equipment management and financial management.

Table 3.

Steps in the process of setting up standard doses.

On the FMECA part, we were able to determine 52 risks. The distribution of the initial criticality was as follows: 44% low criticality, 44% moderate and 12% high criticality. Then, we applied the means of risk control. Thanks to these measures, 46% of the risks were considered acceptable, 52% to be monitored, among these risks we had the storage of finished preparations. Finally, 1 risk remains a major criticality, it is the risk of musculoskeletal disorders in pharmacy workers. We mapped the residual criticality with a Farmer diagram, table 4.

Table 4.

Farmer diagram - Residual criticality of our process.

Risk Control Level (M)	5			3
	4						1
	3			4	1		4	1	4		1
	2		3		6	1	4		2		3
	1	3	1	1	2	1		3	1		2
		1	2	3	4	5	6	8	9	10	12	15	16	20	25
		Initial Criticality (Ci)

To illustrate our approach (extract from our grind table 5 ): for each stage of the process mentioned earlier, we have identified the risk, in this case the risk of MSD during the preparation of the DS, the effects of the failure, deterioration in the health of the handlers, and the cause of the failure, in this case the performance of repetitive movements, increased by the performance of long series of preparations. In terms of scoring, we have estimated a frequency of 3, corresponding to an occasional risk (about once a month) and a severity of 4, as this may eventually lead to a permanent partial disability. The product of the frequency and the severity gives a high initial criticality of 12. Among the risk control actions we have proposed: implementation of a number of preparations made per series, organization of a preparation schedule for the DS and the rotation of the personnel and, the acquisition of an automatic preparation machine. The level of control is 3, corresponding to an average control and we obtain a residual criticality of 36. It is at the end of this process that we asked ourselves about the possibility of postponing the start of mass production.

Table 5.

Extract from our FMECA grid on 2 notorious risks.

Process step	Failure number	Failure mode	Effects of the failure	Effects of the failure	Risk number	Initial rating			Risk reduction measures to be implemented / planned	Type of measure	Residual rating
Process step	Failure number	What are the dysfunctions, the risks that can appear at this stage?	If these risks appear, what will be the consequences?	Why / Because of what these risks appeared?	Risk number	F	S	Initial criticality	What are the means currently in place to prevent these risks?	(preventive, detective, curative)	M	Residual criticality
SD preparation	14	Musculoskeletal disorders	Deterioration of the handlers health	Repetitive movements	14,1	3	4	12	Discussion about number of preparations per series	Preventive	3	36
									Thinking about the organization of the DS preparation schedule	Preventive
									Reflection on the rotation of personnel assigned to manufacturing	Preventive
									Automation acquisition of a handling aid tool	Curative
Storage	17	Non-optimal storage (by INN, dosage, unique number)	Picking errors, loss of time in dispensing	Insufficient space and equipment in the current premises to store finished DS preparations	17.1	3	2	6	Installation of equipment + Identification of storage locations	Preventive	3	18

Dose standardisation of anticancer drugs

The feedback from prescribers was positive overall ( table 6 ): the participation rate was 47% on the survey (N=16). Among the answers, 50% of the physicians declared to practice rounding during the prescription (to the unit, to the ten etc…), 66% knew the concept and 100% of the returns were favourable to its implementation.

Table 6.

Results of local survey (N=16).

Section 1: current prescribing practices

1a: Do you apply additional dose rounding when prescribing? □ Yes: 50% (n=8)

1b: If yes, how? □ Rounding to a whole number (unit, ten, hundred…), 100%

1c: If yes, on which molecules?

□ Cytotoxics 100%

□ Monoclonal antibodies 63% (n=5)

□ Antibody drug conjugate 38% (n=3)

1d: If no, specify: example: rounding already set, no interest, wish to remain as close as possible to the BSA…

Section 2: awareness of dose banding concept2. Are you aware of the concept of Dose Banding or dose standardization? □ Yes 69% (n=11)

Section 3: perception and acceptance of the concept

3.a Would you approve of the implementation of this concept when prescribing?

□ Yes 100% (n=16)

3.b What would be for you the maximum percentage of difference with the initial prescription? –

5% variation for cytotoxics (63% of responses)

–

5 to 10% for monoclonal antibodies (5% rounding: 44% of responses - 10% rounding: 50%)

–

5% for antibody drug conjugate (56% of responses) – Other: 20%

4. What do you see as the benefits of this type of concept? –

Time saving: 63%

–

Cost saving: 44%

–

Streamlining the circuit: 38%

–

Secure preparation and reproducibility: 13

Section 4: suggestion and comments

5: Do you have any suggestions/comments to optimize the prescribing and/or the chemotherapy circuit? (open response) –

Acquisition of a robot to facilitate chemotherapy production

–

Incorporation of the standardisation strategy into a trial for validation purposes

–

Biological tests to be carried out on site (currently outsourced)

–

Encourage early prescribing based on previous day's consultation/questionnaire

–

…

This gave us the confidence to continue our work. We pre-selected 21 anticancer drugs, which exceeded the threshold of 250 preparations per year. We excluded fixed-dose drugs from the outset, and then we presented our approach to standardizing eligible INNs to the institutional medical committee for validation and medical approval. The drugs finally retained for application were: Paclitaxel, Fluorouracil (continuous infusion), Cyclophosphamide, Trastuzumab, Docetaxel, Epirubicin, Irinotecan, Gemcitabine, Trastuzumab Emtansin, Eribulin, Rituximab, Docetaxel, et Vinorelbine. Data for some of these are detailed in table 7.

Table 7.

Examples of anticancer drugs pre-selected for analysis.

Drug name	Type	Quantity over the period	Standard doses (mg)	Standard deviation (%)	Dose range	Theoretical percentage of production coverage	Comment
Paclitaxel	Cytotoxic	5210	96	90–101	[-6% - 5%]	85%
			108	102–112	[-6% - 4%]
			120	113–124	[-6% - 3%]
			132	125–134	[-5% - 2%]
			138	135–144	[-2% - 4%]
			150	145–157	[-3% - 5%]
			168	158–176	[-6% - 5%]
Fluorouracile	Cytotoxic	2829	3200	3050–3350	[-5% - 5%]	90%	Infusers only
			3400	3351–3570	[-1% - 5%]
			3600	3571–3780	[-1% - 5%]
			4000	3781–4200	[-5% - 5%]
			4400	4201–4620	[-5% - 5%]
			4800	4621–5050	[-4% - 5%]
Cyclophosphamide	Cytotoxic	2072	750	725–774	[-3%-3%]	91%
			800	775–824	[-3%-3%]
			850	825–874	[-3%-3%]
			900	875–950	[-3%-6%]
			1000	951–1049	[-5%-5%]
			1100	1050–1149	[-5%-4%]
			1200	1150–1250	[-4%-4%]
Carboplatine	Cytotoxic	1522	x	x	x	x	Excluded due to multiphase dose dispersion
Oxaliplatine	Cytotoxic	1449	110	104–120	[-5%-9%]	97%	Deployment suspended due to medical reluctance and discrepancies identified at the preparation stage
			130	121–136	[-7%-5%]
			140	137–147	[-2%-5%]
			150	148–160	[-1%-7%]
			170	161–178	[-5%-5%]
Trastuzumab	Monoclonalantibody	1884	294	270–330	[-8% - 12%]	96%
			357	331–390	[-7% - 9%]
			420	391–450	[-7% - 7%]
			483	451–531	[-7% - 10%]
			567	532–623	[-6% - 10%]
Trastuzumab Emtansine	AntibodyDrug Conjugate	776	160	151–170	[-6%-6%]	96%
			180	171–190	[-5%-5%]
			200	191–210	[-5%-5%]
			220	211–230	[-4%-4%]
			240	231–250	[-4%-4%]
			260	251–270	[-3%-3%]
			280	271–300	[-3%-3%]
			320	301–340	[-6%-6%]

Among these drugs Paclitaxel is the most widely used molecule in the hospital. We analysed the dispersion of paclitaxel doses; we notice a quasi-normal distribution with a large part of doses between 96 and 168 mg. We have proposed 7 SDs, allowing us to cover 85% of the preparations administered in 2020. So according to our criteria, paclitaxel is eligible for standardization.

For Oxaliplatin, we have identified and proposed 5 SDs, allowing us to cover 97% of the doses administered in 2020. However, physicians have expressed some reservations about the frequency of toxicities observed (neuropathies) and would like to keep the dose adjustment fine-tuned. Moreover, we were also blocked at the preparation stage because we have different volumes of solvents for identical dosages: glucose of 250 or 500 mL depending on the protocols. It is therefore necessary to standardize the volumes and revise the dose intervals for better medical acceptance.

About Carboplatin we notice a multiphase dispersion of doses, due to the diversity of treatments protocols used in different pathologies. In addition, the dose of carboplatin is adapted to each treatment course according to creatinine clearance, which characterizes the patient's renal function. Finally, there is a non-consensual practice of capping doses, depending on the protocols and prescribers this can be 700, 750 and 800 mg. Therefore, because of these different points, Carboplatin is not eligible for standardization as it stands.

Monitoring indicators

Indicators have been determined to monitor this first phase of the implementation of SD workflow.

The first indicator is the ownership of using SD routinely and embed them in habits, by comparing the number of potentially standardizable prescriptions vs. those that were actually standardized, over the period from August 1st, 2021 to January 31, 2022. This rate was 76% over the 6 months, with a rate of 82% at month 6.

Next, we analyzed the number of non-administered preparations returns per month, one year around the standardization launch date, i.e., February 1, 2021 to January 31, 2022. We did not observe any significant change related to the SD, we had between 100 and 150 returns depending on the month, the causes of these variations could be multiple: for example, the periods of school vacations or end-of-year celebrations were associated with a greater number of returns.

Finally, we analyzed the daily activity profile: i.e., the hourly distribution of the activity over the day as well as the proportion of preparation done in advance vs. just-in-time. We studied this indicator over two different weeks, one before and one after the start of the standardization, in a period of full staffing and outside the school vacations. Here again we did not observe any significant difference, we have a production made up of 75% in advance with peaks of activity observed at the beginning of the half-day.

Conclusion

In conclusion, the implementation of the DS at the Curie Institute in Saint-Cloud was carried out with clinical approval of the INNs, doses and standardized intervals. Our work differs somewhat from the feedback found in the scientific literature. Indeed, even if the interest of standardization is no longer to be demonstrated, it implies important changes in the practices of different actors (physicians, nurses, pharmacists, technicians and all the teams involved in the process of chemotherapy prescription/preparation/administration), within an already complex process. We wanted to further secure the deployment of DS in our centre by conducting an a priori risk analysis, with a FMEA.

Ultimately, our approach appears to be in accordance with current international and national guidelines, such as ISOPP recommendations (section 28), or the French “Good Preparation Practices” guide.

Following this analysis, we decided to implement the new circuit in two phases. The first phase started in July 2021 with the activation of the prescription in DS. FMECA matrix appears to be a dynamic tool, which can be updated regularly according to the failures and non-conformities identified after launch. Then, the evaluation of the first indicators shows on the one hand an appropriation of the DS by the doctors and especially do not show any disruption of the existing organization. This reinforces our position for the continuation of the project, with the 2nd phase which will take place in 2025, with the start of mass production, after moving, automation and qualification of our new unit. Automation would not only optimise and secure preparation flows, it would also help control human resources and reduce the risk of MSD.

Footnotes

Acknowledgements

The authors would like to acknowledge teams from the Pharmacy, Medical Oncology and Quality Risk Management Departments, for their advice at every stage of this process.

Author contributions

Khevin Itoua-Gassaye wrote the manuscript and carried out the research as part of his PhD. thesis. Mallory Friou, Laurence Escalup and Romain Desmaris supervised the work, contributed to the project design, and reviewed the manuscript. I confirm that all authors have reviewed and approved the final version of the manuscript.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Data sharing statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

ORCID iDs

Khevin Itoua-Gassaye

Mallory Friou

References

World Health Organization [Internet] . [cited 2022 Aug 14]. Cancer. Available from: https://www.who.int/fr/news-room/fact-sheets/detail/cancer.

ISOPP Standards for the Safe Handling of Cytotoxics . Journal of Oncology Pharmacy Practice 2022 [cited 2025 Sep 19];28(3_suppl):S1-S126.

Infrah

Breton

. Panorama des cancers en France - Edition 2021 [Internet]. Institut national du cancer; 2021 [cited 2021 Dec 26]. Available from: https://www.e-cancer.fr/Expertises-et-publications/Catalogue-des-publications/Panorama-des-cancers-en-France-Edition-2021.

Chiffres clés de la chimiothérapie - Chimiothérapie [Internet] . [cited 2022 Jan 3]. Available from: https://www.e-cancer.fr/Professionnels-de-sante/Les-traitements/Chimiotherapie/Chiffres-cles-de-la-chimiotherapie.

Calmus

Thuong

Morin

, et al. Qualité des soins perçue par le patient – Indicateurs PROMs et PREMs. Haute Autorité de Santé; 2021 p. 134.

Rossinot

de Jésus

Sieradzki

, et al. L’observatoire des attentes des patients : une innovation UNICANCER. Innov ther oncol [Internet]. 2015 Nov [cited 2021 Dec 23];1(2). Available from: https://fr.slideshare.net/HlneRossinot/article-ito-63337039.

Escalup

Hurgon

Chastang

, et al. Apport de la méthodologie LEAN en Hôpital de jour (HDJ) et Unité de production des chimiothérapies (UPAC) : amélioration du parcours patient. In Hyères; 2016 [cited 2021 Dec 26]. Available from: https://www.gerpac.eu/apport-de-la-methodologie-lean-en-hopital-de-jour-hdj-et-unite-de-production-des-chimiotherapies-upac-amelioration-du-parcours-patient.

Pouliquen

Escalup

Jourdan

, et al. Dose standardisation of anticancer drugs. Int J Clin Pharm 2011 Apr 1; 33: 221–228.

Dooley

Singh

Michael

. Implications of dose rounding of chemotherapy to the nearest vial size. Support Care Cancer 2004 Sep; 12: 653–656.

10.

Plumridge

Sewell

. Dose-banding of cytotoxic drugs: a new concept in cancer chemotherapy. Am J Health Syst Pharm 2001 Sep 15; 58: 1760–1764.

11.

Sewell

Kaestner

. Pharmacoeconomic aspects of Dose-Banding. 2006 [cited 2022 Mar 16]; Available from: https://pearl.plymouth.ac.uk/handle/10026.1/3722.

12.

Mayer

. National Health Service England introduces dose banding - The Lancet Oncology. Lancet Oncol [Internet]. 2016 May 26 [cited 2022 Mar 15]; Available from: https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(16)30199-1.pdf.

13.

Fahrenbruch

Kintzel

Bott

, et al. Dose Rounding of Biologic and Cytotoxic Anticancer Agents: A Position Statement of the Hematology/Oncology Pharmacy Association. Journal of Oncology Practice 2018 Feb 5; 8: 130–136.

14.

Kienlin

. Circuit des anticancéreux injectables : parcours de formation par modules de simulation et outils d’évaluation au sein d’une Pharmacie à Usage Intérieur virtuelle [Internet] [other]. Université de Lorraine; 2018 [cited 2022 Mar 18]. p. NNT : 2018LORR2054. Available from: https://hal.univ-lorraine.fr/hal-03297558.

15.

Direction générale de l’offre de soins. Qualité de la prise en charge médicamenteuse : Outils pour les établissements de santé. 2012 Feb p. 45.

16.

Sahli

El Ghardallou

Bougmiza

, et al. Evaluation de la sécurité du circuit des médicaments anticancéreux dans un hôpital régional en tunisie. Pan Afr Med J 2016 Feb 4; 23: 30.

17.

Bonan

Martelli

Berhoune

, et al. The application of hazard analysis and critical control points and risk management in the preparation of anti-cancer drugs. Int J Qual Health Care 2009 Feb; 21: 44–50.

18.

Agence Nationale de Sécurité du Médicament [Internet] . [cited 2023 Feb 11]. Bonnes pratiques de préparation (Edition 2022). Available from: https://ansm.sante.fr/documents/reference/bonnes-pratiques-de-preparation.

19.

Haute Autorité de Santé [Internet] . [cited 2021 Jul 10]. Mettre en œuvre la gestion des risques associés aux soins en établissement de santé. Available from: https://www.has-sante.fr/jcms/c_1239410/fr/mettre-en-oeuvre-la-gestion-des-risques-associes-aux-soins-en-etablissement-de-sante.