PHARMACISTS REGULATIONS
[GOOD MANUFACTURING PRACTICE FOR MEDICINAL
PRODUCTS] 2008
In virtue of the powers vested in me under articles 47a(2) and 62 of the Pharmacists Ordinance
[New Version], 1981,1 (hereafter ― the Ordinance), and, with respect to Regulation 27, with the
approval of the Minister of Finance under Article 39b of the Budgetary Principles Act, 1985, and
with the consent of the Knesset Labor, Welfare and Health Committee, under article 21a(a) of
the Basic Law: the Knesset2 and article 2(b) of the Penal Law, 1977,3 I hereby promulgate the
following regulations:
1.
DEFINITIONS
In these regulations —
“quality assurance” ―the total sum of the organized arrangements made with the object
of ensuring that a medicinal product is effective, safe and of the quality required
for its indications or intended use;
“authorization”―the Director’s authorization for manufacturing or for importation of
medicinal product under Regulation 2(a)or for marketing of medicinal product
under regulation 2(a1);
"a batch" — a defined quantity of a product manufactured in a single manufacturing cycle;
“licensee” — as defined in the Medicinal Products Regulations;
“quality control” —the manufacturer’s sustained control process designed to guarantee that
neither starting material nor finished products are released for manufacture, sale or
marketing, as the case may be, before it has been determined that their quality conforms
to their authorized specifications, as set out in their medicinal product registration file;
“hazardous agents”―chemical, physical or biological agents liable to cause direct or indirect,
acute or long-term injury to health;
"the Director " -- as defined in the Ordinance, to include a member of the staff of the Ministry's
Pharmaceuticals Standards and Control Institute whom the Director has authorized for
the purpose of all or part of these Regulations;
“active pharmaceutical ingredient” (API)―the active chemical or biological substance in a
product causing the actions the product is used for;
"Importation" – as defined in the Commentary Ordinance [new version].5
1
2
3
Laws of the State of Israel , New Version 35, p. 694; Book of Laws, 2002, p.138.
Book of Laws, 1958, p. 69; 2000, p.166.
Book of Laws, 1977, p. 226; 1954, p.348.
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Manufaturing – as defined in the ordinance including partial manufacturing, dividing up of
batches, repackaging, re-labeling, quality control and release of batches and
manufacturing for export only.
“manufacturer”― the owner of a business for manufacturing medicinal products;
“a recognized state” — as defined in the Medicinal Products Regulations;
“quality assurance manager” ― a licensed pharmacist, doctor, chemist, engineer or the
possessor of an academic qualification in the life sciences, appointed to his position by
an authorization holder, and who has at least three years proven experience in quality
assurance in the pharmaceuticals industry;
“recognized laboratory” ― as defined in the Medicinal Products Regulations;
“a business”― a business, including “a health care institution” as defined in the Ordinance,
which manufactures, imports or markets medicinal products;
"marketing" – as defined in the ordinance excluding import and export
“product", "medicinal product” — as defined in the Ordinance excluding medicinal food
products ;
“good distribution practice” (GDP)―all the actions designed to guarantee that a medicinal
product is distributed in conditions which guarantee that, for the whole length of its
distribution chain from manufacturer to end consumer, it meets the quality requirements
laid down in European Directive 2001/83/EC, including amendments to it as shall be
made from time to time;
“good manufacturing practice” (GMP)―all the actions designed to guarantee that a medicinal
product is consistently produced and controlled in accordance with the quality standards
appropriate for its intended use in conformity with the principles and guidelines of
European Directive 2003/94/EC for medicinal products for human use and of
91/412/EEC for veterinary products, and as set out in the European Union’s GMP
guideline (Eudralex, vol. 4), including amendments to it as shall be made from time to
time;
“GMP certificate”― a certificate attesting that its holder is an authorization holder, and which
states the time for the Director’s inspection of his business and that his business meets
requirements;
“Medicinal Products Regulations”― the Pharmacists Regulations [Medicinal Products}, 1986.4
2.
4
MANUFACTURING/IMPORTATION AUTHORIZATION and
marketing authorization
Compendium of Regulations, 1985, p. 906; 2002, p.736.
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(a) No medicinal product shall be manufactured or imported, other than in a business.
holding a manufacturing/importation authorization.
(a1) no medicinal product shall be marketed other than in a business holding a
marketing authorization.
(b) The Director shall not give a manufacturing/importation authorization to a business unless
he is satisfied that it meets all the following conditions:
(1) It has a business license, issued under the Business Licensing Act, 1968, insofar as
that Act applies to it;
(2) It meets the provisions of these Regulations to the Director’s satisfaction;
(3) It is managed by skilled professionals, among them a quality assurance director, a
responsible pharmacist, and a manager or other office holder responsible for
manufacturing in the business, all of whom have the appropriate training for their
duties;
(4) Its products are manufactured in conformity with Good Manufacturing Practice
(GMP);
(5) The Director has inspected the business, such inspections to be carried out
according to the European Commission's procedures "Compilation of Community
Procedures on Inspections and Exchange of Information";
(6) The active pharmaceutical ingredients (API) used in manufacturing medicinal
products are manufactured according to Good Manufacturing Practice (GMP);
(c) The provisions of Clause 2(b)(4) notwithstanding, the Director may grant a
manufacturing/importation authorization to a business which imports medicinal products
exclusively from recognized states if he is satisfied that the medicinal have been
manufactured in accordance with standards which are at least equivalent to the rules of
good manufacturing practice, such as The PIC/S organization’s current guide to GMP
for medicinal products (PE-009) or the United States Rules of GMP set out in CFR 21,
parts 210 and 211.
3.
CONDITIONS FOR GRANTING AUTHORIZATION
(a) The authorization shall specify the name of the authorization holder, detailed
address, , the manufacturing site, medicinal products and the pharmaceutical form
authorized by the Director for that given business.
(b) The Director may make his grant of authorization conditional on the terms set out below,
and may alter or add to them should he be informed of new circumstances:
(1) All manufacturing and marketing is subject to inspection, as the Director shall direct;
(2) The manufacturing of medicinal products is restricted to certain categories;
(3) The business observes standard operating procedures (SOP);
(4) Any other term affecting the work of the business and intended to protect the public
health.
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(c) The Director shall allow the authorization holder a reasonable space of time in which to
take the steps necessary for meeting the conditions specified in Sub-Regulation 3(b)
above, but should he see that postponing the implementation of that Sub-Regulation
endangers the public health, he may order it implemented forthwith, provided only that he
grant the authorization holder the first subsequent opportunity of a hearing.
4.
DURATION OF A manufacturing / importation
AUTHORIZATION
A manufacturing / importation authorization shall remain valid for five years,
the Director being entitled to renew it for further periods not to exceed five years at a time.
5.
APPLYING FOR AND RENEWING A
MANUFACTURING/IMPORTATION AUTHORIZATION
(a) An application for a manufacturing/importation authorization or its renewal shall be
submitted to the Director by a business’s quality assurance manager;
(b) The application shall state the types of medicinal product manufactured at the business,
and include the following appendices:
(1) The basis of design, including the planning principles observed to make the structure
and its systems suitable for the manufacture and storage of medicinal products,
enable cleaning and maintenance processes, and the measures for preventing
contamination, particularly cross-contamination.
(2) Engineering drawings, plan and cross-section, of the business, to include:
(i) The width, length, height, floor area and purpose of every room and section in the
business;
(ii) The location and internal dimensions of all natural ventilation openings and
mechanical ventilation appliances, including their output, filtration levels, pressure
differences, recycled-to-fresh air ratio, and cleanliness levels in the manufacturing
areas;
(iii) The material covering the walls;
(iv) The marking of all sanitary fixtures and appliances, all water-supply and effluent
removal pipes, stating their diameter, slope, and the effluent removal method
used.
(v) The marking of waste containers and waste-storage facilities and their capacity.
(3) A copy of the business’s layout to a scale of 1:100;
(4) Documentation of the measures taken to make the structure suitable, in terms of the
appropriate infrastructure, for the manufacture and storage of medicinal products, as
the Director shall require.
(5) The detailed Curriculum Vitae of the quality assurance manager, responsible
pharmacist and production manager, to include their training and experience in
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manufacturing the types of medicinal products specified in the authorization
application, together with documents corroborating the said data;
(6) Written affidavits from the quality assurance manager, responsible pharmacist and
production manager that they are familiar with the statutory provisions, regulations
and directives relating to the management of a medicinal product business;
(7) A list of the medicinal products to be manufactured, their pharmaceutical form, and the
site of their manufacture;
(8) The plan and description of the business;
(9) Material flow charts;
(10) Personnel flow charts;
(11) Waste flow charts;
(c) Should the Director find that the scale of an aforesaid flow-chart or plan in SubRegulation 5(b)(2) and 5(b)(3) does not show sufficient detail, he may require that it
be submitted to a different scale.
(d) Before carrying out any expansion of, or substantive alteration to, the business, the effect
of which is to alter any data in the application appendices listed in Sub-Regulation 5(b)
above, the authorization holder shall submit to the Director new appendices, as the case
may require, for his authorization.
(e) Sub-regulations 5(b) and 5(c) shall not apply to an authorization renewal application,
provided the following conditions be met:
(1) No substantive changes have been made to the business, its production lines or the
medicinal products manufactured, and the appendices submitted with the original
application still represent the current situation;
(2) The renewal application is accompanied by the quality assurance manager’s written
affidavit that the appendices submitted for the purposes of the original application still
accurately represent the situation obtaining at the time of submission of the renewal
application.
(f) The Director shall give his decision on an authorization or renewal application no more
than 120 days from the application’s submission and, should the application be rejected,
shall issue a reasoned notification accordingly.
(g) Should the Director have required the applicant to submit missing or additional data, the
period of time elapsing until the said data are submitted shall be added to the period of
time specified in Sub-Regulation 5(f) above.
(h) An application for renewal of an authorization shall not be submitted less than 120 days
before the said authorization’s expiry;
(j) Should the Director be of the opinion that an authorization should not be renewed, he shall
so inform the applicant in a reasoned letter 60 days before the authorization’s expiry;
(k) Once an application for renewal of a business’s authorization has been duly submitted, the
expiring authorization shall be deemed extended until the Director’s decision on the
renewal application is known.
5A GMP CERTICATE
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(A)
The Director will issue a GMP certificate to the manufacturing/importation authorization
holder only after ensuring by mean of repeated inspections that the business complies
with all the provisions of these Regulations. The GMP certificate will be issued not later
than 30 days after the completion of the inspection.
(b)
The Director will update the published list of authorized manufacturers after issuing a
new GMP certificate.
6.
The duties of the manufacturing/importation authorization
holder
(a) A manufacturing/importation authorization holder shall not manufacture, market or
store medicinal products other than as specified in the terms of registration for the
said medicinal products or in the terms of his authorization, as the case may be.
(b) The authorization holder shall ensure that his production, marketing and storage
procedures guarantee that the medicinal products manufactured meet accepted standards
of strength, quality and purity, as required by their terms of registration.
(c) Any intended substantive alteration to the production conditions or substantive
alteration in the information detailed in regulation 5, must be notified to the Director.
The Director will decide and issue a written authorization within 90 days.
(d) An authorization holder shall regularly review the production methods in his business in
light of the latest available technologies and scientific knowledge.
(e) An authorization holder shall establish and implement an efficient quality assurance
system in his manufacturing business.
7.
CONTRACTED-OUT PRODUCTION
(a) Any part of the manufacturing according to these regulations not carried out by the
authorization holder himself (hereafter ― contracted-out production) requires the
Director’s prior authorization.
(b) The Director shall not give the said authorization unless he is satisfied that―
(1) The contracted-out production is carried out in accordance with Good Manufacturing
Practice and according to the terms of registration of the medicinal products
manufactured.
(2) There is nothing in the contracted-out production to harm or injure the health or
safety of the public.
(3) The authorization holder and the contracted-out manufacturer have signed a quality
contract. The contract shall clearly define the responsibility of each party and shall
define in particular the observance of Good Manufacturing Practice to be followed by
the contract acceptor and the manner in which the responsible pharmacist for
certifying each batch is to discharge is responsibilities. (
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8.
PREMISES AND EQUIPMENT
(a) All premises and appliances for manufacturing, marketing or storing medicinal
products shall be―
(1) Of a size and layout sufficient for manufacture and storage of the required quality and
safety;
(2) Complete and in sound working order so that manufacture and storage can be carried
on in proper working conditions.
(3) Clean and well-maintained so as to prevent contamination, and cross-contamination
in particular, and also side effects liable to detract from product quality;
(4) Planned so as to minimize the risk of production errors and damage to the quality of
the medicinal products;
(5) Ventilated and air-conditioned so as to maintain the temperature, humidity and level of
cleanliness appropriate to the medicinal products manufactured and stored on the
site.
(b) All critical premises, appliances, systems and equipment used for manufacturing
medicinal products shall undergo validation to ensure that they meet their intended
use.
9.
PERSONNEL
(a)
Any manufacturing, storage and testing of batches of medicinal products shall be
carried out by a sufficient number of professional personnel skilled in the type of
work being carried out.
(b)
The authorization holder shall draw up job descriptions and an organizational chart
for his professional staff in terms of their responsibility for maintaining Good
Manufacturing Practice.
(c)
The authorization holder shall employ skilled professionals, as set out in Regulation
2(b)(3), and shall notify the Director in writing of any change in the said personnel.
(d)
The authorization holder shall ensure that employees in positions of responsibility
for maintaining good manufacturing practice shall follow standard operating
procedures and shall ensure that they are duly trained, instructed and authorized.
(e)
The responsible pharmacist, the quality assurance manager and the production
manager shall ensure that manufacturing in the business is being carried on, at all
times, in conformity with Good Manufacturing Practice and the provisions of these
Regulations.
(f)
The authorization holder shall provide his aforesaid trained professionals all the
resources required for them to carry out their duties.
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10. THE DUTY TO PROTECT OCCUPATIONAL HEALTH AND
MAINTAIN HYGIENE
(a)
The authorization holder shall have clear procedures drawn up on all matters
relating to occupational health, the maintenance of the rules of hygiene, and
correct dress, in order to prevent possible harm to the quality of the medicinal
products. The personnel shall receive training and qualification on these
procedures.
(b)
The authorization holder shall arrange appropriate instruction for all workers at their
time of hiring, and at least once per year subsequently, on the risks to safety,
hygiene and health attached to work with hazardous agents and on methods for
preventing the said risks.
(c)
The authorization holder shall verify that each worker has understood the content
of the aforesaid instruction and that he observes all the instructions and procedures
governing his work with hazardous agents.
11. PRODUCTION CONTROL
(a)
The production department shall control the production process by means of the
following operations including:
(1) Verify compliance with the standard operating procedures (SOP), printed and
authorized in advance, and which in turn conform to Good Manufacturing
Practice;
(2) Sample and test the medicinal product at different stages of the production
process;
(3) Record and investigate every deviation and defect in the medicinal product and
its production process;
(4) Take all possible technical and organizational measures available to prevent
contamination, and particularly cross-contamination, and mix-ups of one
medicinal product.
(5) Check that all production processes are valid and replicable; any new
manufacture or important modification of a manufacturing process of a
medicinal product shall be validated. Critical phases of manufacturing
processes shall be regularly re-validated.
12. QUALITY ASSURANCE AND QUALITY CONTROL
(a)
No one shall manufacture a medicinal product unless he has a working department
of quality assurance (hereafter ― the department) and all the following conditions
are met―
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(1) The department shall be a separate unit, independent of all other production
departments, directed by a quality assurance manager, and answerable only
to senior management;
(2) The department shall have at its disposal recognized quality assurance
laboratories for the purposes of performing the necessary examination and
testing of the starting materials, packaging materials, and intermediate and
finished medicinal products;
(b)
No batch of medicinal product shall be marketed until the department and the
responsible pharmacist have given their authorization. For this purpose,
“authorization” must include approval of the laboratory tests, production
procedures, results of in-process controls, production documentation, process
deviation reports, and the conformity of the medicinal product to the relevant
specifications in the registration file;
(c)
No medicinal product recalled from the market shall be redistributed or repackaged
until laboratory tests have been performed, an adequate documented investigation
has been conducted and the department has issued its authorization.
(d)
Any alteration to the procedures for manufacturing or controlling the quality of a
medicinal product requires the department’s authorization.
(e)
All methods of manufacturing, packaging, distribution and storage liable to affect
the quality of a medicinal product must be tested by the department to its
satisfaction and the department must issue its authorization, confirming that the
methods are professional, appropriate and acceptable, and present no danger to
the health of the public.
(f)
The department is responsible for ensuring that all quality tests are performed in
laboratories, as set out in Sub-Regulation 12(a)(2) above.
(g)
The department shall investigate any complaint regarding the quality of medicinal
products in the business.
(h)
Should the Director see that a quality assurance manager is doing any of the
following ―
(1) Acts in such a way as to harm or risk harming the health of the public or in
violation of these Regulations;
(2) Conducts himself unprofessionally;
(3) Displays lack of responsibility or grave negligence in the performance of his
duties;
(4) Has been convicted of an offence whose nature, gravity and circumstances
are not, in the Director’s opinion, compatible with carrying out quality
assurance duties;
―he may forbid the authorization holder to employ him in his current position
in the business.
(i)
The Director shall not issue such a prohibition under Sub-Regulation 12(h) above
until he has given the authorization holder or the quality assurance manager, as
the case may be, the opportunity of a hearing before the Director; however, should
the Director find that delaying the said prohibition is liable to harm the public health,
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he may issue the prohibition forthwith, provided only that he give the authorization
holder or the quality assurance manager, as the case may be, the first possible
subsequent opportunity of a hearing.
13. DOCUMENTATION
(a)
An authorization holder shall maintain a records system, to include records of all of
the following―
(1) Specifications, manufacturing formulae and processing and packaging instructions;
(2) Procedure and records covering the various manufacturing operations
preformed and the testing of all production batches;
(3) Standard operating procedures for production and quality control in the
business;
(4) Follow-up procedures for all starting materials and other products used in the
production process;
(5) Miscellaneous controls.
(b)
The documents shall enable the history of the manufacture of each batch,
including the changes introduced during the development stage through to
commercial manufacture to be traced, this to include all rejected batches.
(c)
Batch records shall be kept for at least a year after a medicinal product’s expiry
date or at least five years from a medicinal product’s date of manufacture,
whichever is the later.
(d)
For an investigational medicinal product, batch records shall be retained for at least
five years from the end of the last clinical trial in which the batch was used.
(e)
The use of electronic records instead of written documentation shall be permitted
only after the recording system has been validated and the data is shown to be
stored in an appropriate manner, and for a period not less than the period required
under Sub-Regulations 13(c) and (d) above.
(f)
The hardware and software used in electronic recording systems shall be reliable,
and reasonably protected against unauthorized entry, disruption, violation or willful
damage to the records, and furnish a reasonable level of availability, reliability and
data back-up.
(g)
All documents shall be clear, tested, up-to-date and available for inspection by the
Director at all times.
14. RETAINING SAMPLES
(a)
The manufacturing/importation authorization holder shall retain samples of starting
materials, other than solvents, gases and water, used in the manufacturing
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process,, for at least two years from the date of the release of the batch of the
medicinal product; should the stability of the starting material, as stated in the
manufacturing specifications, be less than two years, the retention period for the
samples shall be shortened accordingly; enough of the sample shall be retained to
suffice for two complete tests.
(b)
During testing, the authorization holder shall take and retain samples from every batch
manufactured of a finished medicinal product, to an amount sufficient for two complete
laboratory tests (except for sterility and pyrogenicity tests) for the purposes of future
follow-up and quality testing.
(c)
Test results shall be retained for five years or for one year after the expiry date,
whichever is the later.
(d)
Batch samples shall be retained under authorized storage conditions, as specified in the
product’s registration and the authorization, for at least one year after the expiry date.
(e) For the said duration of their said retention period test results and samples shall remain
available for inspection by the Director.
15. COMPLAINTS AND RECALL
(a)
Every medicinal product authorization holder or licensee shall set up a system for
recording and investigating complaints from the public.
(b)
Every complaint about a defect in the quality of a medicinal product shall be investigated
and recorded by the department; the authorization holder shall notify the Director, or any
other person or body he shall nominate, of every defect that could to lead to an abnormal
restriction in the manufacture or supply of a medicinal product or a recall.
(c)
A manufacturer shall take all measures to enable him to keep track of every batch, and
of the amount of a medicinal product sold, for the purpose of recalling a defective
medicinal product at the Director’s order or should a medicinal product be liable to
endanger the public health.
(d) The marketing of a medicinal product declared defective by its licensee or authorization
holder or by the Director shall be halted immediately and the product shall be recalled to
the wholesaler, or authorization holder, or any other place the Director shall order.
16. SELF INSPECTION
Every authorization holder shall conduct repeated self-inspection as part of his quality
assurance system in order to monitor the implementation of good manufacturing practice
and to take necessary corrective measures as required; the authorization holder shall
record the internal audits and every corrective measure subsequently taken.
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17.
(a)
THE RESPONSIBLE PHARMACIST
The responsible pharmacist shall be a licensed pharmacist who has acquired
practical experience of at least two years in a business which has been authorized
to manufacture medicinal products, in the activities of qualitative and quantitative
analysis of active substances and medicinal products, and of the testing and
checking necessary to ensure the quality of medicinal products. The qualified
person in medical gases manufacturing plant could have a degree in chemistry or
chemistry engineer and not a licensed pharmacist.
(a1) notwithstanding The provisions of Clause 17(a), a licensed pharmacist approved by
the Director as a responsible pharmacist in a business of manufacture or import of
medicinal products prior to the coming into effect of these regulations, and who
acted as a responsible pharmacist in this business, can continue to hold this
position.
(b)
The responsibilities of the responsible pharmacist are:
(1) to ensure that each batch of medicinal product released for marketing has
been manufactured and tested in accordance with the provisions of the Medicinal
Products Ordinance and Regulations and in conformity with the product’s terms of
registration.
(2) to certify in a register that each batch of medicinal product released for sale
satisfies the provisions of this regulation, to keep this register up to date for a
period of at least 5 years;
To have the register available for inspection by the Director at all times.
(3) in the case of medicinal products coming from third countries with whom Israel
does not have a mutual recognition agreement, to ensure that each batch of
medicinal product released for marketing has undergone a full qualitative analysis,
quantitative analysis of at least all the active substances and all the other tests or
checks necessary to ensure the quality of medicinal products in accordance with
the requirements of the marketing authorization.
(4) In the case of a business of manufacture/importation of investigational
medicinal products, in accordance with regulation 18,
(a) to ensure that each batch of investigational medicinal product released
for use in humans is manufactured and tested according to the protocol of the
clinical trial, according to the principles of Good Manufacturing Practice and in
accordance to these regulations.
(b) to certify in a register that each batch of medicinal product released for
sale satisfies the provisions of this regulation, to keep this register up to date for a
period of at least 5 years.
To have the register available for inspection by the Director at all times.
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(c) Should the Director see that a responsible pharmacist is doing any of the
following ―
(1) Acts in such a way as to harm or risk harming the health of the public or in violation
of these regulations;
(2) Conducts himself unprofessionally;
(3) Displays lack of responsibility or grave negligence in the performance of his duties;
(4) Has been convicted of an offence whose nature, gravity and circumstances are not,
in the Director’s opinion, compatible with carrying out pharmacists' duties;
―he may forbid the authorization holder to employ him in his current position in the
business.
(d) The Director shall not issue such a prohibition under Sub-Regulation 17(c) above until he
has given the authorization holder or the responsible pharmacist, as the case may be,
the opportunity of a hearing before the Director; however, should the Director find that
delaying the said prohibition is liable to harm the public health, he may issue the
prohibition forthwith, provided only that he give the authorization holder or the
responsible pharmacist, as the case may be, the first possible subsequent opportunity of
a hearing before him.
18. INVESTIGATIONAL MEDICINAL PRODUCTS
(a)
The provisions of these regulations shall apply mutatis mutandis to investigational
medicinal products with respect to the progress of the developmental and clinical
trial stages the product is intended to undergo; the critical stages in the products’
development, such as the sterilization stage, shall be validated; all an
investigational product’s development and production stages shall be fully
recorded; nonetheless, as from Phase III an investigational medicinal product’s
manufacturing site , or import of an investigational medicinal product, requires
manufacturing/import authorization.
(b)
An investigational medicinal product shall be marked and packaged so as to ensure―
(1) its safety and quality;
(2) its proper use by a trial participant;
(3) its identification and the identification of the trial the investigational product belongs
to.
(c)
Together with the trial’s sponsor, the authorization holder shall set up a data collection
system on the use of the investigational product, to include complaints, side effects,
defects and breakdowns, and shall notify the Director of all said data relating to the
manufacture and use of the investigational product.
19. A DRUGS WHOLESALER
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The provisions of these Regulations shall apply mutatis mutandis, and in accordance with a
directive to be drawn up, to a drugs wholesaler, with regard to the activities he engages in, ,
and the types of medicinal products he markets.
20. GOOD DISTRIBUTION PRACTICE
An authorization holder shall ensure that his business complies with the rules of Good
Distribution Practice (GDP).
21. OVERSIGHT POWERS
In order to maintain oversight over the implementation of the provisions of these regulations
the Director may ―
(1) having identified himself, enter any place where starting materials or medicinal products
are manufactured, held or offered for sale in order to inspect them and their production
process and whether the provisions of these regulations have been observed; however,
the Director shall not enter a place used for residential purposes only, other than by court
order;
(2) require any person concerned in the matter to hand over to him information and
documents regarding the starting materials and medicinal products;
(3) take samples of the starting materials and medicinal products in a quantity sufficient for
performing various tests, and do with them as he sees fit; the samples shall be handed
over to the Director without payment;
(4) seize starting materials and medicinal products, prohibit their manufacture and sale, or,
should it be feared that they are harmful, or may be harmful, to the public health, destroy
them.
(5) carry out repeated inspections, notified or unnotified, of the business.
22. WITHOUT LET OR HINDRANCE
No one may refuse the Director entry to premises where medicinal products are manufactured,
or hinder or delay the Director’s said entry, himself or by means of another person, nor shall he
decline to display on demand the whole stock of medicinal products, starting materials and
samples in his possession or control, nor the records and registers he is duty bound to
maintain, nor other documents the Director shall require, which pertain to his business dealings
in starting materials and medicinal products.
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23. REVOKING AN AUTHORIZATION
(a) Should the Director see that a business is acting in a manner actually or potentially
harmful to the public health or in violation of these Regulations or in violation of the terms of its
authorization, he may prohibit the manufacture or sale of any medicinal products, seize and
destroy them at need, and may revoke, suspend or refuse to renew the said authorization.
(b) has the director revoked, suspended or refused to renew an authorization, the gmp
certificate will be revoked as well;
©
the director will update the published list of authorized manufactures or importers on
every revoking of a GMP certificate.
24. THE DIRECTOR’S POWERS
The Director shall not seize or destroy starting materials or medicinal products or issue a
directive under Regulations 21 and 23 above until he has given the authorization holder or the
licensee, as the case may be, the opportunity of a hearing before him; however, should the
Director find that delaying the said directive is liable to harm the public health, he may issue the
directive forthwith, provided only that he give the authorization holder or the licensee, as the
case may be, the first possible subsequent opportunity of a hearing before him.
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25. OBJECTIONS TO THE DIRECTOR’S DECISIONS
(a)
Anyone who considers themselves injured by a decision under these Regulations may,
within thirty days of receiving written notification of the decision, submit a formal
objection to the Director in accordance with a directive to be drawn up;
(b)
The objection shall be submitted in writing and may be accompanied by a professional
opinion and documentation supporting the arguments made in it;
(c)
Within thirty days of receiving notification of the objection or within thirty days of hearing
the objector set out his arguments, whichever is the later, the Director shall issue his
reasoned decision in writing;
(d)
The Director shall not reject an objection, in all or in part, without giving the objector a
reasonable opportunity to have his arguments heard, provided the objector has
requested this in submitting the objection.
26. REPORTING AN INCIDENT
Should the Director hear of an incident which he is convinced it is important for him to be
informed about, he may require an urgent report to be submitted to him, within a period of time
he shall set.
27. FEES
(a)
The fee for the services listed in Column 1 of the First Schedule shall be as listed in
Column 2 of the schedule.
(b)
The size of the fees listed in the Sixth Schedule shall change on 1 st January of each year
(hereafter ― the change day) by the amount of the rise in the new index over the base
index.
(c)
The amount of a fee that changes as aforesaid shall be rounded to the nearest whole
shekel.
(d)
In this Regulation ―
“index” ― the Consumer Price Index published by the Central Bureau of Statistics;
“the new index” ― the last index published before the change day;
“the base index” ― the latest index published before the previous change day, and for
the purpose of the first change day after these Regulations come into force, the
latest index published before their coming into force.
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28. RESTRICTIONS ON APPLICATION
(a) These Regulations shall not apply to ―
(1) A pharmacy preparations dispensed for a customer/patient by a pharmacist in a
hospital in accordance with a doctor’s or dentist’s or veterinarian’s prescription;
(2) Manufacture in a medical laboratory or academic institution for the purposes of
teaching, research or analysis;
(3) Legal activities of a pharmacy.
(b) With the consent of the Director and on the terms of that consent, these Regulations shall
not apply to the manufacture of a medicinal product in a period of emergency for the
protection of the public against chemical, biological or nuclear attack, or to a product
protecting against an epidemic disease so designated by the Minister of Health in
accordance with the Public Health Ordinance, 1940.
29. NON-INFRINGEMENT OF EXISTING LEGISLATION
The powers under these Regulations do not derogate from the powers under any other
legislation, and meeting an obligation under these Regulations confers no exemption from an
obligation under any other legislation.
30. COMING INTO EFFECT
These Regulations shall come into effect one year from the day of their publication.
31. TRANSITION PERIOD PROVISIONS
An authorization holder or licensee who before these regulations came into effect had received
authorization for good manufacturing practice shall be deemed to have the same authorization
under these Regulations until the expiry date of the said authorization.
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FIRST SCHEDULE
(Regulation 27)
FEES
Column 1
Column 2
Service
In NIS
(1) Application for Authorization
35,000
(2) Application for copy of GMP certificate
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Signed
This ____ day of ________, 2008
______________________
Ya’akov Ben-Yizri
Minister of Health
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