PHARMACEUTICAL TECHNOLOGY AND BIOPHARMACY 2
Lecture 1 – introduction
Product care ensures availability of the proper medicine, in the right dosage form, of
good quality for the patient at the time of administration.
Purchasing – stock management – storage – compounding (if applicable) –
dispensing – patient counselling
Compounding involves the customization of medications for patients based on
individual needs, such as adjusting dosage forms. Dispensing is the process of
providing patients with the prescribed medications. Patient counselling involves
providing information and guidance to patients about their prescribed medications.
Pharmaceutical care = patient care + product care
Medicine: a pharmacologically active substance (drug substance, API) manufactured
into a suitable dosage form (drug product).
The dosage form consists of the active compound plus excipients. Excipients
are part of each formulation in order to:
Facilitate production
Improve quality of the product
Optimize performance of the product
Increase patient acceptability and compliance
API and dosage form determine biopharmaceutical properties.
Biopharmaceutics are therefore leading for the dosage form and the route of
administration.
Systemic action: The API is absorbed into the bloodstream and reaches its
site of action via the bloodstream. The pharmacological effect occurs throughout the
whole body. This involves biopharmaceutics and ADME. Systemic drugs can have
side effects, as they affect not only the target site, but also other tissues and organs.
Adverse effects may arise due to interactions with off-target receptors or unintended
physiological responses.
Local action: API is administered at the site where it should act. The drug acts locally
without systemic absorption into the bloodstream. Local administration minimizes the
risk of systemic side effects because the concentration of the drug at the site of
action is higher compared to its concentration in the bloodstream.
Legal status of medicines –
Pharmaceutical preparations (branded products):
Commercially available
Industrially manufactured
Licensed
1
, Independent supervision (government, national inspection)
Licensed: marketing authorization granted from competent (bevoegde) authorities,
based on safety, quality and efficacy.
Extemporaneous pharmacy preparations:
Prepared on demand (prescription)
Tailor-made for the patient (personalized medicine)
Unlicensed
Independent supervision lacks
Additional responsibilities are required from professional health care workers to
assure quality (prescribing, preparation).
Dutch Medicines Act: pharmacist is allowed to prepare a drug product for patients
in own pharmacy.
Dutch Health and Youth care Inspectorate: framework for pharmacy preparations.
Royal Dutch Pharmacists Association KNMP:
Guidelines for pharmacy preparations
Pharmacotherapeutically rational, good design
Dutch Pharmacist’s Formulary (FNA)
- Standardized formulations, general procedures
With ‘design’ the combination of API and excipients is meant.
Pharmacy preparations: personalized medicine!
This is the ‘manufacture’ of unlicensed pharmaceutical preparations by or at the
request of pharmacies or other healthcare establishments.
The pharmacist is legally allowed to prepare and dispense pharmaceutical dosage
forms in response to a health practitioner’s prescription when the pharmacist is
competent by education, training and practice.
Why pharmacy preparations?
To optimize pharmacotherapy for a patient
- Commercial products insufficiently meet specific requirements.
- Commercial products are unavailable.
- Tailor-made approach.
To increase patient compliance (adherence)
- More flexibility
- Better acceptance by the patient (convenience – ease and comfort with
medication regimen)
2
,When pharmacy preparations?
Dose adjustment
Dosage form adjustment (other route of administration)
Hypersensitivity to excipients
Unavailability of a product on the market
Modification of industrial preparation
Short shelf life
Investigational medicinal product - pharmaceutical product that is under
investigation or is studied as part of a clinical trial.
When a medication has a short shelf life, it can’t be prepared in stock. An example is
radio pharmaceuticals (otherwise radioactivity is gone).
Types of pharmacy preparations –
Compounded from raw materials
- Drug substance + excipients.
Manipulated (commercially available) licensed dosage form
- E.g. Pulverizing tablets to make capsules.
Preparation prior to use: handling procedures to ready a pharmaceutical
product for administration.
- E.g. reconstitution of injection fluid: Some injectable medications are
provided in a powder. Before administration, pharmacists need to
reconstitute these medications by adding a specified amount of diluent to
the vial.
- VTGM = voor toediening gereedmaken
Quality assurance of the final product is done with the European Pharmacopoeia.
This contains a monograph about pharmaceutical preparations with the essential
requirements for the most common dosage forms. It does not contain monographs
for individual preparations.
Quality assurance in production is done with good manufacturing practice (GMP).
From prescription to dispensing –
1st choice: commercially available preparation
2nd choice: pharmacy preparation (personalized medicine)
Standardized: following protocols
Non-standardized: no protocols
Risk assessment:
Benefit for patient
Possible risk related to quality level
There is a responsibility for both prescriber
and pharmacist for patient treatment.
3
, Standardization –
Standardization is applicable for routinely made pharmacy preparations. The design
of composition and preparation method is developed and validated in advance. Each
batch, prepared according to the corresponding procedure and formula, has the
desired (high) quality.
Batch size
Composition
Preparation method
Materials and equipment
In-process and end- controls are done. Any deviation should be validated.
The Dutch Pharmacist’s Formulary (FNA) provides standardized formulations and
general procedures.
Formulation
Preparation method
Storage, packaging, leaflet
Background information (effectiveness, safety, stability)
Non-standardization –
No formulation readily available
Single patient (or few patients)
Before preparation:
- Evaluation of effectiveness, safety and quality
- Risk assessment
Design and production process drafted from scratch
- Minimum set of quality requirements (stick to general procedures as much
as possible)
- Consider practical applicability, ease of use, safety for patient and
compounder
Product file:
Pharmacotherapy
Specifications of drug substance and excipients
Design of the formulation and preparation
Equipment (incl. standard operating procedures (SOPs))
Trial preparation (first try out)
Test results
Criteria for release
Stability
Storage conditions
Packaging, labelling, patient information
The preparation record contains all information relevant for the preparation and
manufacture process.
4
Lecture 1 – introduction
Product care ensures availability of the proper medicine, in the right dosage form, of
good quality for the patient at the time of administration.
Purchasing – stock management – storage – compounding (if applicable) –
dispensing – patient counselling
Compounding involves the customization of medications for patients based on
individual needs, such as adjusting dosage forms. Dispensing is the process of
providing patients with the prescribed medications. Patient counselling involves
providing information and guidance to patients about their prescribed medications.
Pharmaceutical care = patient care + product care
Medicine: a pharmacologically active substance (drug substance, API) manufactured
into a suitable dosage form (drug product).
The dosage form consists of the active compound plus excipients. Excipients
are part of each formulation in order to:
Facilitate production
Improve quality of the product
Optimize performance of the product
Increase patient acceptability and compliance
API and dosage form determine biopharmaceutical properties.
Biopharmaceutics are therefore leading for the dosage form and the route of
administration.
Systemic action: The API is absorbed into the bloodstream and reaches its
site of action via the bloodstream. The pharmacological effect occurs throughout the
whole body. This involves biopharmaceutics and ADME. Systemic drugs can have
side effects, as they affect not only the target site, but also other tissues and organs.
Adverse effects may arise due to interactions with off-target receptors or unintended
physiological responses.
Local action: API is administered at the site where it should act. The drug acts locally
without systemic absorption into the bloodstream. Local administration minimizes the
risk of systemic side effects because the concentration of the drug at the site of
action is higher compared to its concentration in the bloodstream.
Legal status of medicines –
Pharmaceutical preparations (branded products):
Commercially available
Industrially manufactured
Licensed
1
, Independent supervision (government, national inspection)
Licensed: marketing authorization granted from competent (bevoegde) authorities,
based on safety, quality and efficacy.
Extemporaneous pharmacy preparations:
Prepared on demand (prescription)
Tailor-made for the patient (personalized medicine)
Unlicensed
Independent supervision lacks
Additional responsibilities are required from professional health care workers to
assure quality (prescribing, preparation).
Dutch Medicines Act: pharmacist is allowed to prepare a drug product for patients
in own pharmacy.
Dutch Health and Youth care Inspectorate: framework for pharmacy preparations.
Royal Dutch Pharmacists Association KNMP:
Guidelines for pharmacy preparations
Pharmacotherapeutically rational, good design
Dutch Pharmacist’s Formulary (FNA)
- Standardized formulations, general procedures
With ‘design’ the combination of API and excipients is meant.
Pharmacy preparations: personalized medicine!
This is the ‘manufacture’ of unlicensed pharmaceutical preparations by or at the
request of pharmacies or other healthcare establishments.
The pharmacist is legally allowed to prepare and dispense pharmaceutical dosage
forms in response to a health practitioner’s prescription when the pharmacist is
competent by education, training and practice.
Why pharmacy preparations?
To optimize pharmacotherapy for a patient
- Commercial products insufficiently meet specific requirements.
- Commercial products are unavailable.
- Tailor-made approach.
To increase patient compliance (adherence)
- More flexibility
- Better acceptance by the patient (convenience – ease and comfort with
medication regimen)
2
,When pharmacy preparations?
Dose adjustment
Dosage form adjustment (other route of administration)
Hypersensitivity to excipients
Unavailability of a product on the market
Modification of industrial preparation
Short shelf life
Investigational medicinal product - pharmaceutical product that is under
investigation or is studied as part of a clinical trial.
When a medication has a short shelf life, it can’t be prepared in stock. An example is
radio pharmaceuticals (otherwise radioactivity is gone).
Types of pharmacy preparations –
Compounded from raw materials
- Drug substance + excipients.
Manipulated (commercially available) licensed dosage form
- E.g. Pulverizing tablets to make capsules.
Preparation prior to use: handling procedures to ready a pharmaceutical
product for administration.
- E.g. reconstitution of injection fluid: Some injectable medications are
provided in a powder. Before administration, pharmacists need to
reconstitute these medications by adding a specified amount of diluent to
the vial.
- VTGM = voor toediening gereedmaken
Quality assurance of the final product is done with the European Pharmacopoeia.
This contains a monograph about pharmaceutical preparations with the essential
requirements for the most common dosage forms. It does not contain monographs
for individual preparations.
Quality assurance in production is done with good manufacturing practice (GMP).
From prescription to dispensing –
1st choice: commercially available preparation
2nd choice: pharmacy preparation (personalized medicine)
Standardized: following protocols
Non-standardized: no protocols
Risk assessment:
Benefit for patient
Possible risk related to quality level
There is a responsibility for both prescriber
and pharmacist for patient treatment.
3
, Standardization –
Standardization is applicable for routinely made pharmacy preparations. The design
of composition and preparation method is developed and validated in advance. Each
batch, prepared according to the corresponding procedure and formula, has the
desired (high) quality.
Batch size
Composition
Preparation method
Materials and equipment
In-process and end- controls are done. Any deviation should be validated.
The Dutch Pharmacist’s Formulary (FNA) provides standardized formulations and
general procedures.
Formulation
Preparation method
Storage, packaging, leaflet
Background information (effectiveness, safety, stability)
Non-standardization –
No formulation readily available
Single patient (or few patients)
Before preparation:
- Evaluation of effectiveness, safety and quality
- Risk assessment
Design and production process drafted from scratch
- Minimum set of quality requirements (stick to general procedures as much
as possible)
- Consider practical applicability, ease of use, safety for patient and
compounder
Product file:
Pharmacotherapy
Specifications of drug substance and excipients
Design of the formulation and preparation
Equipment (incl. standard operating procedures (SOPs))
Trial preparation (first try out)
Test results
Criteria for release
Stability
Storage conditions
Packaging, labelling, patient information
The preparation record contains all information relevant for the preparation and
manufacture process.
4
