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Determination of the carbon footprint of morphine tablets and morphine solution for injection – a collaboration between Amgros and the Capital Region Pharmacy

European Statement

Selection, Procurement and Distribution

Author(s)

Bitten Abildtrup, Lone Deleuran, Mira Dysgård, Nina Müller, Sofie Pedersen, Trine Schnor, Ulrik Wøldike

Why was it done?

It is estimated that medicine contribute 20% of the Danish regions total CO2e emissions. Amgros and the Hospital Pharmacies of Denmark are committed to develop carbon reduction initiatives to assist the regions CO2e reduction strategy. It is essential to identify the main contributors of CO2e emissions in the lifecycle of a drug to support CO2e reduction.

What was done?

The Danish procurement organization Amgros I/S is responsible for buying medicine for Danish public hospitals. As part of the ambition for sustainability, The Capital Region Pharmacy (RAP) in collaboration with Amgros has made a bottom-up hotspot life cycle analysis (hLCA) of the carbon-footprint of morphine in tablets and solution for injection. The hLCA identified the main CO2e emission factors from API/excipient production to administration of the drug.

How was it done?

The energy consumption of the production processes was mapped at RAP. Five reference flows were modulated (tablets in three types of primary packaging and solution for injection in two types) and reported. The hLCA data for the API was extracted from literature while data for the excipients and packaging material were calculated using Ecoinvent. Ecoinvent is a life cycle inventory database used to support environmental assessments of products and processes.

What has been achieved?

The preliminary conclusion of the analysis shows the largest CO2e emissions per DDD originates from administering the drug due to the use of single-use materials.
Leaving out administration of the drug, the main CO2e emissions from tablets are API production and packaging materials. Packaging materials are the main CO2e contributor for the solution for injection.
The end report of the LCA was available, end of autumn 2023.

What next?

The hLCA’s are being used internally in Amgros to develop criteria for tenders. The hospital pharmacies can use the hLCA calculations to identify key subprocesses where reduction of the CO2e footprint is greatest.
The results contribute to:
• Danish hospital pharmacies better understand the CO2e emissions when prescribing and administering medicines
• Dialogue with the pharmaceutical industry about their CO2e emissions hotspots
Finally, the results will hopefully encourage other countries to incorporate environmental criteria in future medicinal tendering process for medicines.

Optimising the process for incoming requests for new extemporaneous products

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European Statement

Production and Compounding

Author(s)

Mette Lethan, Tove Hansen, Louise Rasmussen Duckert, Trine Schnor

Why was it done?

In the clinic, a need for a NEP, as either a change in an existing product or a new formulation, may arise. Requests are risk assessed by the Hospital Pharmacy Drug Information Centre (DIC) before production is initiated. However, there was no clear process for handling requests, resulting in prolonged process times. NEP may require searching for new raw materials, new packaging or developing of a new formulation, which are time consuming tasks. Therefore, the wish to optimise the process arose.

What was done?

A procedure for handling requests for new extemporaneous products (NEP) in a Good Manufacturing Practice (GMP) regulated production was developed to improve success rate and aligning the process.

How was it done?

A small unit was formed with the purpose of handling requests for NEP. The unit consists of academics employed in the production department with expert knowledge about both sterile and non-sterile production.
A standard operating procedure was formed, in collaboration with DIC, which included a form, to be filled out with information needed for handling the request. This includes drug formulation, strength and dosage, along with any specific requirements.
The unit evaluates the request – is it possible for us to manufacture, sterile or non-sterile, are raw materials available in appropriate quality, analysis requirements, and stability of the product. The evaluation is made in communication with departments like Purchasing, Quality Control/Assurance, Stability as well as the relevant production department.
If a positive outcome, the request is given to the production department, to finalise production. If the outcome is negative a rejection is sent to the requester with a reason.

What has been achieved?

Based on data from the last three years, we now know how many requests we receive, which type of products are requested, processing times, and which products were made and why/why not.
There is a clear path of communication into the pharmacy and between relevant departments, ensuring that essential pharmaceuticals will be developed in a timely manner or a justified rejection is sent enabling the clinic to look for alternatives.

What next?

Some products are difficult to handle, such as cytostatics, antibodies and hormones. Next step is to investigate these product types.

A new vancomycin formulation for oral use

European Statement

Production and Compounding

Author(s)

Mette Lethan, Tove Hansen, Trine Schnor, Louise Rasmussen Duckert

Why was it done?

Oral vancomycin 125 mg four times a day for 10 days, is the common treatment for antibiotic-associated clostridium difficile colitis. As solid oral formulations are unsuitable due to strong diarrhea, an i.v. formulation in a diluted form (10 mg/ml) is used. However, several issues with that use, required the need for creating a new formulation.
The product is used for treatment of kids and adults, often with nausea. The low strength requires large volumes of solution and with no flavoring the liquid is very bitter.
Furthermore, the current solution has a limited stability causing difficulties as it is often desired to treat the patients at home. Therefore, a wish arose for a new formulation with a higher concentration, better stability and improved organoleptic qualities.

What was done?

A new oral formulation of Vancomycin was developed to improve the treatment of antibiotic-associated clostridium difficile colitis. The new formulation consists of the active ingredient (API) Vancomycin as a powder with a solvency for dissolving prior to use.

How was it done?

To obtain the best stability it was selected to make a new formulation consisting of a premeasured API, with a solvency ready to mix before use, to obtain a final strength of 50 mg/ml and a volume equivalent to 48 hours of doses.
Vancomycin in pharmacopeia quality was acquired and analyzed. A solvency was formulated mostly consisting of water, conservation and orange flavoring. A test was conducted with a weighed-out API to ensure that it was dissolvable with the solvency in the selected packaging.

What has been achieved?

A product achieving the wanted changes was tested and made. Making a formulation consisting of a premeasured powder creates the possibility of a higher durability. When mixed with the flavored solvency, the wanted strength is achieved.
The new formulation can be stored at room temperature before dissolving. It can be dissolved by the patient before use and kept refrigerated until the full volume is used. The product is easy for the patient to handle and therefore enables treatment in the patients own home.

What next?

A new product was made. Final use by patients will be tested for ease of use and potential home treatment.

DEVELOPMENT OF A STANDARDISED PAEDIATRIC PARENTERAL NUTRITION FOR THE FIRST DAYS OF LIFE OF A TERM OR PRETERM NEWBORN

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European Statement

Production and Compounding

Author(s)

Isabelle Sommer, David Palmero, Céline Julie Fischer-Fumeaux, Lydie Beauport, Vincent Adamo, Hervé Schwebel, Pascal Bonnabry, Lucie Bouchoud, Farshid Sadeghipour

Why was it done?

PN can be composed of about 50 different ingredients, whereof the majority are amino acids (AA). Therefore, PN represents a complex and high-risk fabrication. ME are often related to PN and may include prescription, transcription, preparation, and administration errors. As the treatment with PN is indispensable for a good cerebral and neurologic development as well as a postnatal weight gain, ME can result in growth retardation, developmental disturbances, and infections.
This project was performed with the aim to reduce ME having an impact on vulnerable newborns and to improve the security and quality of their nutritional treatment.

What was done?

A standardized pediatric parenteral nutrition (PN) solution for the first days of life of newborn infants has been developed. An industrial partner manufactures the ready-to-use double-chamber bag which is available 24/7 and of high-quality allowing a secured administration as well as a reduction of medication errors (ME).

How was it done?

A working group composed of pharmacists, clinicians, neonatologists, and industrials developed a PN solution for the first days of life of newborn infants conforming to the needs of two different neonatal services. An applied standardized PN and the ESPGHAN guidelines haven been used as references. The feasibility of an industrial production of double-chamber bags has been evaluated and implemented.

What has been achieved?

The developed PN solution has been formulated for a peripheral venous administration with an osmolarity under 900 mOsm/L to allow a wider range of application. The production of double-chamber bags has been chosen to increase the stability and shelf-life. The first compartment contains an AA admixture and the second compartment contains glucose and electrolytes (sodium, calcium, organic phosphate). This solution is initially produced by the service of pharmacy and afterwards by the industrial partner. The standardized PN bag has been implemented successfully on the neonatal ward in March 2019. Since then, almost 1800 standardized bags have been used (appr. 90 bags/month), resulting in a reduction of individual on-ward PN preparations of nearly 80%.

What next?

Further standardized PN for newborn infants need to be developed to allow a safe nutritional treatment. On-ward PN preparations must be prohibited to prevent undetectable preparation errors.

DIAZOXIDE 10MG/ML ORAL SUSPENSION AS A COST-EFFECTIVE ALTERNATIVE TO THE COMMERCIAL PREPARATION (submitted in 2019)

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European Statement

Production and Compounding

Author(s)

Beatriz Sánchez Sanz, Iván González Barrios, Siria Pablos Bravo, Sara Ortiz Pérez, Cristian Rosas Espinoza, María Arrieta Loitegui, Francisco Martínez de La Torre, Dolores Canales Sigero, José Miguel Ferrari Piquero

Why was it done?

The objective is the elaboration of a formulation as a cost-effective alternative to the diazoxide oral suspension not commercialised in Spain, to treat patients with hyperinsulinaemic hypoglycaemia.

What was done?

Diazoxide is the first line therapy in infants with hypoglycaemia due to hyperinsulinism. A formulation to facilitate the dosage in newborns has been developed due to the increasing demand at our Hospital.

How was it done?

To evaluate the solubility, a research on Pubmed was executed including terms such as “diazoxide AND solubility” and “tiazides AND solubility”. To determine the stability, the agreement approved by the “Pharmacotechnics Group of the Spanish Society of Hospital Pharmacy” concerning the viability of the non-sterile oral formulations was reviewed. In terms of effectiveness, a retrospective observational study was conducted. Demographic and clinical (duration of the therapy and blood sugar levels 24 hours after first administration, sorted as “sensitive” if those levels were over 60mg/dL) variables were collected.

What has been achieved?

Carboxymethyl cellulose gel 1.5% (CMC) was evaluated as suspending agent, with adequate results. The steps to compounding the formulation of diazoxide 10mg/mL oral suspension were: 1. Four capsules of 25mg were opened and spread over a mortar. 2. 10ml of CMC was measured on a test tube. 3. CMC was added slowly over the powder while stirring the mixture to obtain a homogenized milky creamy. 4. Suspension was stored in an amber bottle. Following our stabilities studies and the lack of preservatives, an expiration date of seven days at ambient temperature was assigned. In our hospital, seven neonates (four males) aged 5.8±2.3 days have been treated with this oral suspension, for an average period of 28 days. Six of them were classified as “sensitive” with levels of 105±30mg/dL while one showed no improvement. Analysing the global expense, one pack of 100 capsules costs €21. Thus, 1 unit of our suspension 10mL cost €0.84 versus 1 bottle of 30mL (€473); the savings are remarkable.

What next?

The preparation constitutes a suitable alternative by using a simple and cheap technique since its introduction. In the future, full studies of stability must be designed to prolong its period of validity and monitor its security.

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