Regulations relating to the manufacture of medicines in pharmacies


Date FOR 2001-06-26-738


Ministry of Health and Care Services


Published in 2001 Booklet 8


Commencement 01/07/2001

Edited

FOR-2009-12-18-1839 from 12/01/2010

Changes


For
Norway

Legal

LOV-2000-06-02-39-§7-1, LOV-2000-06-02-39-§7-2, LOV-2000-06-02-39-§7-3

Promulgated
07/03/2001

Short Title
Regulations on production of medicines in pharmacies

Chapter Overview:

Chapter 1. General provisions (§§ 1-3)
Chapter 2. Manufacturer license (§§ 4-11)
Chapter 3. Quality requirements, durability labeling, claims, etc. (§§ 12-15)
Chapter 4. Requirements for good manufacturing practice (§§ 16-24)
Chapter 5. Commencement (§25)

Adopted by Health and Social Affairs (now the Ministry of Health) on 26 June 2001 pursuant to the Law of 2 June 2000 no. 39 on pharmacy § 7-1, first paragraph, § 7-2 second paragraph and § 7-3 third paragraph.
Changes: Amended by regulation 18 Dec 2009 No.. 1839.

Chapter 1. General Provisions

§ 1. Scope These regulations apply production of medicines in pharmacies. The Norwegian Medicines Agency may make it a condition for manufacturing authorization to other businesses involved in similar manufacture that regulation wholly or partly apply accordingly.

§ 2. Definitions In this regulation:

A)

Manufacturing: Manufacturing, packaging, repackaging, labeling, re-labeling and release of drugs, as well as the necessary checks in connection with these activities. All operations involved in the production and control from receipt of raw materials to the approval of the finished product, and dispensing of finished product or commodity is considered manufacturing.

B)

Resepturproduksjon: Manufacturing of drug for the individual case.

C)

Bearing Manufacturing: Manufacturing of drug to stock and not resepturproduksjon.

D)

Resepturleieproduksjon: Resepturproduksjon where medicine is sold to other independent pharmacies.

E)

Commodity: Substance used in manufacture.

F)

Done Product: that has undergone all stages of production, and which are controlled and released for use.

G)

Intermediate: Produced material must undergo one or more sub-processes to be finished product.

H)

Bulk Product: A product that needs to be filled, packaged or labeled in order to become a finished product.

I)

Batch: A defined amount of raw material, packaging or product being produced in a process or series of processes so that it is expected to be homogeneous.

J)

Batch number: A unique name, for example. figure number, for a particular batch.

K)

Final inspection: The checks to be made before the responsible pharmacist approves the drug for use.

L)

Quarantine: The status of an item that is separate physical or other effective means, pending a decision on release or rejection.

M)

Eligibility: Steps to demonstrate that the equipment works properly and gives expected results.

N)

Validation: Prove, in accordance with the principles of GMP, that procedure, process, equipment, material, activity or system provides expected results.

§ 3. Exemption from requirement Norwegian Medicines Agency may grant exemptions from the requirements of this Directive if this is warranted by special reasons and deemed necessary to ensure sound and prudent drug supply.

Chapter 2. Manufacturer permit

§ 4. General fabrication A pharmacy may only produce drugs if it has manufacturing authorization for the current pharmacy.
Manufacturer permits are not required for basic istandgjøring of drugs because of limited durability must be prepared just before disclosure. The same goes for broaching and other simple istandgjøring of medicines with marketing authorization. Such simple capable allowances considered part of expedition work and must be documented.
For manufacture of radiopharmaceuticals also requires permission from the Norwegian Radiation Protection Authority.

§ 5. Tilvirkertillatelsens scope Where the requirements of this regulation are met, the manufacturer license include:

A)
resepturproduksjon,

B)
resepturleieproduksjon,

C)
stock production, or

D)
sale of stock production to wholesalers or other pharmacies.

Manufacturing permissible scope shall be indicated in the permit, including any limitations in the pharmaceutical formulations that might be produced.
Permit shall apply to a specific pharmacy.

§ 6. Terms Norwegian Medicines Agency may impose conditions for granting manufacturing authorization under subsection if special circumstances and considerations of manufacturing nature and extent dictate.


§ 7. Application for manufacturing authorization application for manufacturing authorization must be submitted to the Norwegian Medicines Agency.
In the application the applicant shall provide the information necessary to show that the requirements of the manufacturing authorization are fulfilled, including information on:

A)
which drug the desired produced.

B)
which drug the desired produced for warehousing.

C)
which pharmaceutical formulations as desired sold to other pharmacies and wholesalers.

D)
overview of the organization and responsibilities related to the manufacture, including information about who applied for as control pharmacist.

E)
details of purchases and control of raw materials for use in legemiddeltilvirkningen.

F)
information about quality control of medicines to be made, including the use of subcontractors for such services.

G)
details of the premises to be used in the manufacture.

§ 8. Approval of control Pharmacist Pharmacy with manufacturing authorization referred to in § 5, first paragraph b, c and d, shall have control pharmacist. Control Pharmacist and any deputy shall be approved by the Norwegian Medicines Agency, and should have education equivalent pharmaceutical candidate.

§ 9. Amendment of the manufacturer permit Changing tilvirkertillatelsens scope and terms, including the change of control pharmacist, must be approved by the Norwegian Medicines Agency.

§ 10. Revocation of manufacturing authorization Norwegian Medicines Agency shall withdraw all or part of the manufacturer permit:

A)
by deliberately false or incomplete indication of the place of manufacture or the pharmaceutical formulations manufactured,

B)
by significantly violating the requirements of premises, technical equipment and control facilities in the manufacture of products, or

C)
if the manufacturer no longer has at his disposal an approved inspection pharmacist.

Norwegian Medicines Agency may revoke or modify manufacturer Authorisation

A)
if the applicant has provided false information in the application for manufacturing authorization, or has failed to notify changed circumstances for authorization

B)
breach of conditions set the manufacturer authorization

C)
in the manufacture of other premises or other medicines or pharmaceutical formulations than those covered by the permit,

D)
by failure to meet the requirements in the regulations of the organization staff and to put control pharmacist able to perform their duties,

E)
for failure to meet obligation,

F)
for failure notifications about undertaken replace control pharmacist,

G)
by insufficient documentation or certification in accordance with the requirements for the manufacture of medicines in pharmacies or by inadequate compliance with the manufacturing operations following marketing authorization, or

H)
breach of statutory control requirements.

Decisions pursuant to subsections may be temporary or definitive.

§ 11. The delivery Agreement on resepturleieproduksjon must be designed so that the manufacturer is obliged to deliver any drug covered by the manufacturer license. For drug delivery urgent duties resepturleieprodusenten to deliver the goods as soon as possible, usually within the next business day.

Chapter 3. Quality requirements, durability labeling, claims, etc.

§ 12. Quality requirements and requirements for final inspection Manufacturing of pharmaceuticals must comply with the provisions of Chapters 4 and provisions in the current pharmacopoeia.
Drugs manufactured in pharmacies and raw materials used in production must have a quality that is in accordance with provisions of the relevant pharmacopoeia.
The drugs should be subject to an adequate analytical final inspection. By resepturproduksjon medicines exempt from Pharmacopoeia general requirements for analytical final inspection. Such production shall be subject to quality assurance as otherwise ensure compliance with quality requirements for medicines.
Product Control in accordance with current pharmacopoeia shall be made by fabricating dosed drugs where dosage accuracy and bioavailability are important parameters.
Products with active substances that are highly hygroscopic or readily crumble should be checked, for example. the density determining resolutions.
It shall carry out a quantitative determination of active substances for the following product groups:

A)
dosed drugs, with the exception of suppositories, where a single active compound is contained with amounts of 50 mg or less.

B)
Suppositories.

C)
trituration, extracts and diluenda of potent substances.

D)
Dilutions of acids, ammonia, etc. for medical use.


§ 13. Commodity and packaging control quality of raw materials incorporated in legemiddeltilvirkningen and quality of packaging that has direct contact with the product must satisfy the requirements of pharmacopoeia.
When procuring raw materials are analyzed and possibly inflicted identity guarantee of supplier shall pharmacist ensure that the provider has the necessary permits for such manufacture. If such permission is not available, the pharmacist otherwise ensure that raw materials are of satisfactory quality.

§ 14. Durability Marking Apoteket must affix information about the durability of all drugs that they manufacturer. Shelf life is determined by the individual product chemical, physical and microbiological properties. Medicines should satisfy farmakopékrav and any product within all the prescribed shelf life.
By resepturproduksjon the resistance maximum set at six months.

§ 15. Complaints and recall of manufactured drugs Pharmacies shall immediately register and investigate complaints on products that have been manufactured in the pharmacy or purchased from other pharmacies. The investigations shall be documented. Or quality defects which can be dangerous to health must be reported to the Norwegian Medicines Agency. The notification requirement also applies if there is suspicion of error.
Pharmacies shall have a system that makes it possible to revoke the drugs immediately and at any time.

Chapter 4. Requirements for good manufacturing practice

§ 16. General requirements Compliance with the provisions of Chapter 4 shall be adjusted manufacturing scope, characteristics and risk factors, including the scope of the manufacturer permit.
Pharmacy with manufacturing authorization shall establish a quality system that documents that business is conducted in accordance with these regulations.
Quality assurance system must be based on specifications for raw materials, packaging, intermediates and finished products, the main regulations regarding the composition, manufacture and control of intermediates and finished goods, as well as instructions for procedures regarding equipment, hygiene, production and control. The system must document that intentional product quality is achieved and could provide a direct traceability throughout the manufacturing process, from the initial match finished product.

§ 17. Staff Operating licensee is responsible for the manufacture of drugs in the pharmacies operating license covers.
By resepturproduksjon shall pharmacist be responsible for the individual production.
In stock production and resepturleieproduksjon shall normally a pharmaceutical candidate be responsible for production. In special cases, the person with different professional backgrounds accepted by the Norwegian Medicines Agency. Control Your pharmacist will release drugs for use.
Responsibilities and organizational issues should be clarified in job descriptions.
Teaching and supervision of the staff shall be sufficient to ensure that products manufactured achieves planned quality.

§ 18. Lease premises shall be designed and dimensioned such that the risk of confusion of products and for cross contamination is sufficiently low relative to manufacturing nature and scope.
The premises shall be sufficiently lighted, heated and ventilated. Air purity and replacement frequency must be adapted to manufacture nature and scope.
In pharmacy with permission resepturproduksjon should production facilities be clearly delineated against the remaining pharmacy premises in a manner that prevents contamination of the manufactured drugs.
Pharmacies authorized stock production and resepturleieproduksjon should normally have locks that separate production facilities from the other pharmacy premises. In floodgates will staff could shift work clothes and cleaning goods. The locks must not be used for purposes other than those that are naturally interlock.
Premises shall be designed and surface treated so that all hygiene instructions can be followed.

§ 19. Equipment Equipment shall be dimensioned and designed so that it is suitable for the manufacture of the drug forms which manufacture license. The equipment must be easy to clean. There should be written procedures for the use, maintenance and inspection of production equipment. Periodic checks must be documented.
Equipment used for production and control shall be satisfactory eligible.
Aseptic procedures should be checked regularly.
Local exhaust and fume hoods used in the preparation of products that have a high risk of contamination of the environment should be placed outside the manufacturing premises.


§ 20. Hygiene There should be written hygiene instructions adapted pharmacy's activities and local conditions, including instructions for cleaning of premises and equipment, handling of raw materials and products, personal hygiene, hygienic working techniques, use of protective clothing and any person sluice and Precautions infectious diseases.
Hygiene instructions should be regularly reviewed and monitored by the entire staff.

§ 21. Documentation for stock production will be prepared main regulations for each product and for each batch size. Main regulations shall consist of preparasjonsforskrift, dispensing regulation and control regulation. Main regulations shall be uniquely detailed designed and adapted for the staff to follow it. The various control points during the presentation must be clearly indicated, cf. § 23 on quality control.
Main regulations shall be inspected and authorized by the person in charge of production and control.
Working label for each batch must be a copy of the relevant part of the main regulations, designed so that transmission errors are eliminated. Working paper shall contain:

A)
name and the batch number.

B)
detailed representation regulations.

C)
control number used raw materials and packaging.

D)
dates for the various stages of preparation with signature of the operator and any inspector.

E)
indication of executed process controls, including dividends scrutiny and control of labels.

F)
dated signature of the production charge.

G)
chemical, physical and any microbiological analysis results.

H)
dated signature of release for the sale of control pharmacist.

When fabrication is a dispensing commodity or bulk product, the main regulations consist of dispensing regulation and control regulation.
Shall be kept production journal.
Documentation retained for at least one year beyond the product's shelf life, yet not less than five years. Main regulations that are no longer in use shall be kept as long as the work slip from last production.

§ 22. Documentation for resepturproduksjon Each product shall continuously assigned a control number. The product control number and durability shall be indicated in the product label.
All production takes place in accordance with the work slip. Work Banknotes for products manufactured by resepturproduksjon kept for at least one year.
Working paper shall contain:

A)
A copy of the prescription or main regulations designed so that transmission errors are eliminated.

B)
complete preparation regulation, which expresses the method used in the preparation. Important steps in the fabrication should be documented.

C)
Any steriliseringstid, sterilization temperature and other conditions associated with preparation of sterile drugs must be documented in the working paper.

D)
Any calculations, detailed reproduced.

E)
Control Number raw materials used.

F)
Documentation of balance.

G)
Accurate reproduction of product labeling.

H)
Manufacturing Date.

I)
Dated signature of the person who made the product and, where the product is manufactured by a pharmacist, the pharmacist who approves product. By resepturleieproduksjon shall control pharmacist approve the product.

§ 23. Requirements for production
1)
There shall be written procedures for all general operations, including the production of the common dosage forms, used sterilization methods and the like.

2)
Production will take place after the main regulations, appropriate procedures or instructions.

3)
Critical steps of the manufacturing process shall be validated if this is required in view of the type of production and scope.

4)
During production will manufacture vessels and installations must be clearly marked with the name and the batch number.

5)
All tradeoffs should double checked. Where the weighing equipment with printer used, control of printer printout be such a control.

6)
It should normally only work with one product at a time in the same room. If several products anyway processed simultaneously, the production will take place in such a way that cross-contamination and mixing is prevented.

7)
Before manufacture begins shall work zone and equipment be clarified so that there are no residues from other production that can lead to confusion or contamination. The preparation must be documented. It must be shown special care to prevent confusion during dispensing and labeling inventory-production.

8)
containers containing intermediates and bulk products should be labeled with unique name and batch number, and stored safely.

9)

Drogeekstraksjoner or went mixtures must be manufactured in its own premises where there takes another type of manufacturing.

10)
Aseptic produced medicines to be prepared under conditions that provide the necessary security for the sterility is obtained in the finished product.

11)
Preparation of cytostatics should take place in a private room and under conditions which aim to protect both product and staff.

§ 24. Quality Control Laboratory with permission to stock production and resepturleieproduksjon should have an established quality control function which controls pharmacist is responsible. Control Pharmacist is the only one who can release a product for use in production or for sale.
There shall be an ongoing journal of received raw materials and the individual commodity should be assigned to a commodity control number. The control number will make it possible to back trace the product to the individual commodity batch at the supplier and the identity verification item has undergone.
Aseptic techniques should be periodically checked by simulating an aseptic preparation using bacteriological nutrient medium.
In stock production and resepturleieproduksjon following applies:

A)
Control Your pharmacist is responsible for receiving inspection of raw materials, packaging and labels. The goods should be kept in quarantine until they are released for production. Guidelines for this should be found in separate instructions.

B)
The quality control shall also include control of production, control analyzes (including sampling), reference stock and following up complaints. There is still no requirement for reference stock at resepturleieproduksjon.

C)
Where required a quantitative, microbiological or possibly another final inspection of a product, outsiders laboratories used for analysis missions. If the test assignment is performed by an external party, make this mission happen according to a written agreement. The agreement must specify the parties' roles and responsibilities.

D)
In stock production will amount finished product evaluated against theoretical yield, consumption of raw materials, labels and packaging. For large or abnormal deviations that may be of importance to the quality of the product, not the product is released for sale without having found an adequate explanation for the discrepancy.

E)
When taken out reference samples of finished products to these stored at correct storage temperature for the product. The samples should be kept as long as the working paper.

F)
Before release for sale should the finished product are kept separate in quarantine.

Chapter 5. Commencement

§ 25. Commencement These Regulations shall enter into force on 1 July 2001.