The amendments made with the “Regulation Amending the Regulation Regarding the Packaging and Labeling of Medicinal Products for Human Use” published in the Official Gazette dated 30.05.2009, with No. 27243, have been highlighted in italics.

Regulation Regarding the Packaging and Labeling of Medicinal Products for Human Use

PART ONE
Objective, Scope, Legal Basis and Definitions

Objective
Article 1- The objective of this Regulation is to set forth the procedures and principles regarding the information that must be contained on the label and in the package as well as the package insert to ensure the identification and correct use of medicinal products for human use in terms of the health and safety of the persons who will use the registered/permitted medicinal products for human use.

Scope
Article 2- This Regulation shall comprise the minimum compulsory information and conditions that must be contained on the label, packaging and package inserts of medicinal products for human use and real persons or legal entities that have applied for registration/permit and/or who have been granted a registration/permit.

Legal Basis
Article 3- This Regulation has been prepared on the basis of Law No. 1262 on Pharmaceutical and Medicinal Preparations, dated 14/05/1928, clause (k) of paragraph one in article 3 of Principal Law No. 3359 on Health Services, dated 7/5/1987 and article 43 of Decree Law No. 181 on the Organization and Duties of the Ministry of Health, dated 13/12/1983;
In line with Directive 2001/83/EC on medicinal products for human use, for the purpose of ensuring harmonization with the relevant legislation of the European Union regarding medicinal products for human use.

Definitions
Article 4- For the purposes of this Regulation, the following definitions shall apply: Ministry: The Ministry of Health, Medicinal Product for Human Use/Product: Any natural and/or synthetic-based   active substance or combination of substances administered to human beings with a view to treating and/or preventing a disease, making a diagnosis or restoring, correcting or modifying physiological functions, International Non-proprietary Name/INN: The international name of an active substance, accepted or suggested by the World Health Organization, that does not have international proprietorship and should not be used in brand registration in line with the rules of the World Health Organization,
Common name: The common or scientific name of the product which will prevent it from being confused,
Name of the medicinal product for human use: The common or scientific name which will prevent the confusion of the product with INN or the common name, is an invented name and is accepted by the Ministry and is taken as basis in registration/permit,
Unit amount of the medicinal product for human use: The quantitative amounts of the active substance/substances contained in the unit dose, unit volume or unit weight of the product, depending on the pharmaceutical form,
Pharmaceutical Form: The presentation form of the medicinal product manufactured according to its purpose of use,
Outer Package: The package into which the immediate package is placed,
Immediate package: The container in which the product is placed or the form of package directly in contact with the product,
Labeling: Information on the immediate or outer package,
Instructions for Use: Written information presented with the product, prepared for the users,
Summary of Product Characteristics (SPC): The summary of the product characteristics contained in the medicinal product’s registration dossier.
Active substance: The pharmacological active substances used in medicinal products for human use, Excipient: Substances included into the composition of the product, aside from the active substances/substances,
Manufacturer or importer: Real or judicial person having the manufacture or import license for the medicinal products for human use,
Data matrix: Data matrix type two-dimensional barcode,
Legible information: Descriptive content information written under or near the identifier for the purpose of demonstrating the content relating to the barcode or data matrix to the users.
Expiration Date: Date information showing the end of the end of shelf life determined according to the storage conditions of the products during analyses made and within indicators written in the form of year, month, day in numbers or when written openly month in writing, year in numbers or month and year in numbers.

PART TWO
Outer Package, Immediate Package and Package Insert

Outer Package
Article 5- The following shall appear on the outer package or, in case it is not included on the outer package, the immediate package of the product:

a)  The name of the medicinal products for human use, the unit dose, pharmaceutical form and whether they are intended for babies, children or adults, where necessary, shall be indicated. In case the product contains up to three active substances, the INN, or in the absence of the INN, its common name shall be used.

b)  The unit amounts or route of administration and the weight or volume amounts according to the pharmaceutical forms of all active substances indicated with their INN or common name shall be indicated.

c)  The units such as the number of tablets, ampoules, bottles contained in the package shall be indicated numerically as unit amount; whereas the active substances in the pharmaceutical form which cannot be regarded as net content, shall be indicated as volume or weight or dose number; excipients such as coloring matters, preservatives, antioxidants, flavoring substances and alcohol will be indicated in name:

1)  The net amount shall be indicated in aerosols; the number of doses and the dose per spray shall be specified for metered-dose inhalers.

2)  The amount of substances in large-volume parenteral solutions shall be indicated in millimole.

3)  Where possible, also the milligram or gram values corresponding to the international unit (IU) shall be written.

4)  The number of drops per milliliter shall be indicated for products administered orally in drops.

5)  The net content in grams shall be indicated for semi-solid pharmaceutical forms such as ointments and creams.

6)  In packages used via a beaker and which contain a beaker, the formula shall be indicated as dose per beaker ad the weight or volume of the amount of product per beaker shall be indicated.

7)  The formula of the product in the form of ampoules, vials and single-dose injectors shall be indicated as the amount per millimeter or in the whole package. The same rule shall apply for injectable products in powder or concentration and used upon being dissolved in a solvent.

d)  The excipients  known  to  have an evident  effect  and  are  indicated  on the  guidance  specified  in paragraph one of article 19 of this Regulation shall be presented as a list.  However, if the product is injectable or is locally applicable or is an ocular preparation, all excipients shall be indicated.

e)  The method and, if necessary, the route of administration shall be indicated. The required space shall be left for indicating the prescription dose.

f)  The special warning stating: “Keep in its package, in a place that cannot be seen and reached by children”.

g)  Where available, other special warnings relating to the product shall be indicated.

h)  The storage conditions, and if any, the special storage conditions of the product will be indicated.

ı)   Special  warning  relating  to  the  disposal  of  unused  products  or  wastes  of  products  and,  where necessary, the appropriate collection system shall be indicated.

i)   The symbol of recyclable package, the number and abbreviation of the type of package shall be indicated on the packages as per the Regulation on Packaging and Package Wastes published on the Official Gazette dated 24/06/2007, with No. 26562. Except for the products mentioned under the title of Radiopharmaceuticals in this regulation, the management of the wastes of immediate, outer and transportation packages which are not classified as medical and hazardous wastes shall be conducted within the scope of the referred regulation.

j)   The name and address of the registration/permit holder shall be included on the package of the product. If desired, the emblem of the original company and the name and/or logo of the company authorized by the registration/permit holder and marketing the product may be included on the packages of all registered products in Turkey.

k)  The name and address of the manufacturer shall be indicated.

1)  The registration/permit number of the product will be indicated. m) The batch number shall be included.

n)  The expiry date shall be indicated clearly in accordance with the size and characteristics of the immediate package, with the month written in numbers or letters and the year only in numbers,

o)  In case it is a product which is used for self-medication purposes, relevant instructions for the users shall be provided.

ö)  The warnings: “Do not purchase packages that have been cut or opened”, “Read the package insert before use”, “Consult your doctor if any undesirable effects appear” as well as other warnings issued by the Ministry shall be included.

p)  A statement indicating whether the product is or is not subjected to a prescription shall be included.

r)  In order to ensure the traceability of the products legible information regarding the data matrix and its content are included. Registration/permit holders shall apply legible information regarding the data matrix and its content on the outer package in such a way that they can be read by data matrix readers in accordance with the standards mentioned in the data matrix application guide to be issued in connection with this Regulation. Data matrix is included on prescription and non-prescription drugs, borderline products subjected to reimbursement and medical nutritional products subjected to reimbursement, including those which have hospital packages. Data matrix may not be placed on products which are to be consumed within the reimbursement procured by tender by the Ministry. Legible information regarding the data matrix content shall be written legibly and in accordance with the form mentioned in the related guide. In case the information to be included on the package is included in the legible information in accordance with the mentioned form, the same information does not need to be written in another place on package. In the information in the data matrix expiry date may be used as year, month and day, last day of the month in numbers.

s)  The product barcode maybe used. However if there is a data matrix together with the label on the product, information regarding its cancellation is included on the label.

ş)  Price information maybe included on the product packaging.

Immediate Package
Article 6 - Except for the particulars indicated in clauses (a) and (b) of paragraph two of this article and clauses (o), (ö), (p) and (s) of paragraph one of article 5 of this Regulation, immediate packages shall bear the properties and information indicated in article 5 of this Regulation.

Provided that conformance is achieved with paragraph one of this article, the following shall apply in particular;

a) In immediate packages in the form of blisters;

1) The name of the product as laid down in clause (a) of paragraph one of article 5 in the Regulation,

2) The name or emblem of the registration/permit holder,

3) Expiry date written openly as month and year in numbers or month in writing and year in numbers,

4) The batch number.

b) In immediate packages which are too small to contain the properties and information designated for labeling in article 5 of the regulation, the following shall be included;

1) Where possible, the name or emblem of the registration/permit holder,

2) The name of the product; where necessary, the dose and route of administration,

3) Expiry date written openly as month and year in numbers or month in writing and year in numbers,

4) Batch number,

5) Weight, volume or unit unit/amount content,

6) Route of administration.

The current packages of products with no outer packages, shall comply with article 5 of the Regulation. The batch number shall be included in the immediate packages.

See-through Transparent Outer Packages
Article 7 – It is not mandatory to apply labeling on see-through transparent outer packages. However, in this case, all of the information to be contained on the outer package shall be included on the immediate package.

Instruction for Use
Article 8- The package insert shall be prepared in accordance with the SPC of the product, in a manner that is understandable by the user and will fulfill the following:

a)  For the purpose of identifying the product;

1)  The name of the medicinal products for human use, the unit dose, pharmaceutical form and, whether they are intended for babies, children or adults, where necessary, shall be indicated; if the product contains only one active substance and bears an invented name, it shall be used along with its common name.

2)  The unit amounts or route of administration and the weight or volume amounts according to the pharmaceutical forms of all active substances indicated with their INN or common name shall be indicated.

3)  The units such as the number of tablets, ampoules, bottles contained in the package shall be indicated numerically as unit amount; whereas the active substances in the pharmaceutical form which cannot be regarded as net content shall be indicated as volume or weight or dose number.

4)  The therapeutic group or the type of efficiency shall be indicated in terms which are to be easily understood by the patients.

5)  The name and address of the registration holder and manufacturer of the product will be provided.

b)  The areas where it is used in treatment (the therapeutic indications) shall be indicated. c)  The following shall be indicated as relevant information before using the product;

1)  Cases where it should not be used,

2)  Descriptions relating to its use,

3)  Interactions with other medicinal products for human use or other interaction types that may influence the effect of the medicinal product for human use (e.g.; alcohol, tobacco, food),

4)  Warnings relating to  specific patient groups such as children, pregnant or breastfeeding  women, elderly and people in special pathological conditions,

5)  Where available, the effect of the product on driving vehicles and using machinery,

6)  Special warnings relating to excipients that have are important in terms of the safe and effective use of the product,

d)  The following shall be provided as general and relevant information for the correct use of the product;

1)  The amount to be used (Dosage),

2)  The method and, where necessary, the route of administration,

3) The administration frequency of the product upon indicating also that it is to be used where necessary or the right time when it is to be used,

e)  The following shall be indicated in relation with the structure of the product;

1)  Where necessary, the time when the treatment should be interrupted, the duration of the treatment,

2)  The symptoms to be observed, the measures to be adopted and the relevant emergency interventions in case of overdose,

3)  The steps to be taken in case one dose or more doses are not taken,

4)  Where necessary, information regarding the risks that may arise in case of interruption of the use of the product.

f)  The undesired effects to arise during the normal use of the product and the measures to be adopted in case of such a condition; and information on the need to consult one’s doctor or pharmacist in case of any

undesired effect not indicated in the package insert.

g)  The following shall be specified along with the statement emphasizing that the expiry date in indicated on the label;

1)  Warning indicating that it should not be used after this date,

2)  The storage conditions,

3)  Where necessary, warning against an evident degradation/variation in the product,

4)  The full qualitative composition upon using the common names for the presentation of each medicinal

product for human use (in the active substances and excipients) and the quantitative composition in the active substances,

5)  The pharmaceutical form and the content as the weight, volume or dosage unit for each product presentation,

6)  The name and address of the manufacturer.

h) The date when the package insert was last updated shall be provided.

Upon considering that the therapeutic indications of the product and some information relating to the product may give rise to severe drawbacks for the patients, the Ministry may decide to not include it into the package insert.

Terms for Labeling
ARTICLE 9 – The information mentioned in articles 5, 6 and 8 are written on the label in a legible, clearly understandable and unerasable form and attached on the package on an appropriate place so that it cannot fall off.

On products, which sold outside reimbursement organizations where no prices or no current prices are included on the packages, surcharge labels and the current prices of products are placed at pharmacies.”

Symbols and Other Information
Article 10 – The outer package and the package insert may include symbols describing the information indicated in articles 5 and 8 of this Regulation and other information which are beneficial for the users and are in compliance with the SPC of the product, provided that they are encouraging and are not promotional in nature.

The particulars relating to the symbols and information mentioned in paragraph one of this article shall be arranged with the guidance indicated in paragraph one of article 19 of the Regulation.

Information on Promotional Samples
Article 11 – The following shall apply for the products to be used for promotion in accordance with the provisions  of the  Regulation Regarding the Promotional Activities of Medicinal Products for Human Use, published on the Official Gazette dated 23/10/2003, with No. 25268.

“a) They have to comply with the terms indicated in this Regulation. However no barcode or data matrix is placed on the packages of these products.

b) They shall contain a reduced amount. However, this term shall not be sought in promotion samples of

the products which cannot be reduced due to technical reasons.

c) The statements "promotion sample, not for sale" shall be included on the outer package of the promotion samples covering one side. In cases where printing is possible the same statements are included in the immediate package.

Solvents
Article 12 – Also the products which are placed on the market as a solvent alone or to be used with another medicinal product for human use shall comply with the provisions of this Regulation. Regarding solvents which are presented in the same package with any medicinal product for human use, the name and/or formula of the solvent and its net content shall be indicated on the outer package and the package insert.

Products with a Restricted Period of Use
Article 13 – The duration of use and storage conditions of products with a restricted period of use upon being dissolved, diluted or opened shall be separately indicated on the package.

Other Conditions Relating to Packages
Article 14 – In case all the information requested in articles 8 and 10 of this Regulation are not indicated on the immediate or outer package of the product, the presence of the package insert shall be mandatory. Where necessary, also the materials for using the product shall be provided along with the package insert.

Sterile  products  shall  be  marked  as  “sterile”  and  apyrogeneous  products  shall  be  marked  as “apyrogeneous” on the outer and immediate packages and the package insert.

For the purpose of preventing confusion and mistakes, an evident difference in color and/or height shall be ensured at relevant places in the packages of products which are similar in terms of pharmaceutical form and presentation and have a different unit dose.

The information relating to the outer package, immediate packages and the package insert shall be in Turkish for the market placement of the product. However, where necessary and requested one of the official languages of the EU member countries can be used despite Turkish on the outer packages, immediate package and package insert.

However, in case the outer and immediate packages cannot be prepared in Turkish, the package to be prepared in Turkish in accordance with article 8 of this Regulation shall be included at all means and the label bearing the information indicated in article 5 of this Regulation shall be adhered on a suitable place so as not to come off. Not preparing a Turkish immediate package is only acceptable if there is an outer package conforming to article 5.

Application
Article 15 – The following shall be conducted in the applications for registration/permit;

a) Two samples or drafts of the outer and immediate package and the draft package insert prepared for the placement of the product in the market shall be submitted to the Ministry.

b) In case the outer package, label and the package insert of the product is not compliant with the information indicated on this Regulation or the SPC, the Ministry shall reject the application for registration/permit.

c) The variations planned to be made on the outer package, label or the package insert and are included into the scope of this Regulation even though they are not encompassed by the SPC, shall be presented to the Ministry. In case the Ministry does not grant approval within ninety (90) days as of the application date, the applicant may implement the variation.

d) The Ministry’s rejection of the request for registration/permit in accordance with clause (b) or a variation to be made on the outer package, label or package insert according to clause (c) shall not relieve the manufacturer or, where necessary, the registration/permit holder from his/her legal responsibilities.

e) Applications for outer package, label and package inserts prepared in accordance with this Regulation are not refused.

In registered/permitted products, the variations planned to be made on the outer package, label or the package insert and are included into the scope of this Regulation even though they are not encompassed by the SPC, shall be presented to the Ministry. In case the Ministry does not grant approval within sixty (60) days as of the application date, the applicant may implement the variation.

Distribution
Article 16 – No matter how it is distributed (such as retail, wholesale, tenders) each product shall comply with the provisions of this Regulation. However, some additional information in acquisitions to be made by public healthcare institutes and institutions may be used in labeling, provided that they are not in violation of this Regulation.

Registration/permit  holders shall  use  transportation  packages during the  shipment  of  more  than one product so as to ensure product reliability. The transportation packages may be in the form of packs, parcels, boxes or bundles and may be placed inside one another. The amounts to be contained by transportation packages shall be designated at reasonable levels so as to ensure that they may be carried until the final destination without being opened during the sale.

On the transportation packages, there shall always be an identifier containing the information defining the transportation package or an identifier containing all the data matrix information of the products inside the transportation package. The identifiers to be placed on the transportation package shall be applied as indicated in the barcode implementation guidance to be issued in relation with this regulation.

In cases where it is problematic to apply data matrix on product packages due to their properties, the transportation packages of products that can be sold in a multiple quantity shall be data-matrixed as a single product. In such a case, the prices of these products will be designated upon multiplying the prices determined for unit products with the quantity. The prices with the transportation packages of this type of products shall be separately published with unit prices on the price list published by the Ministry.

PART THREE
Radiopharmaceuticals

Radiopharmaceuticals
Article 17- The package of the medicinal products for human use containing radionuclides shall be labeled in accordance with the regulation regarding the Turkish Atomic Energy Agency and other relevant international legislations.

The label on the shielding shall comply with article 5 of this Regulation, except for the provisions set forth in clauses (f), (ı), (o) and (p) in paragraph one of article 5. Furthermore, the label on the shielding shall fully describe all codings. The radioactivity sign, the amount of radioactivity per dose or per vial, specific activities, the calibration date (time and the time zone), the number of capsules, or, for liquids, the amount of milliliters in the container shall be indicated.

The vial shall be labeled with the following information:

a) The name or code of the medicinal product for human use, including the name or chemical of the radionuclide and its chemical symbol,

b) The batch identification and expiry date,

c) The international symbol for radioactivity, d) The name and address of the manufacturer,

e) The particulars specified in paragraph two of this article.

Package Insert of Radiopharmaceuticals
Article 18- It is mandatory to include a detailed package insert into the package of radiopharmaceuticals, radionuclide generators, radionuclide kits or radionuclide precursors.

The package insert shall be prepared in compliance with article 8 of this Regulation. This brochure shall also contain any special measures to be adopted by the administrator and the patient during the preparation and administration of the product and the warnings for the adequate disposal of unused parts or packages.

PART FOUR
Various and Final Provisions

Guide Article 19- The Ministry shall publish in the form of a guidance the general principles to be

complied with where necessary and in relation with the following;

a) The preparation of warnings for some product categories,

b) The preparation of special information for users in case of products to be used for self-medication purposes,

c) The comprehensibility of the Package and Label information,

d) The identification methods, the content of identifiers to be included on outer packages and transportation packages and the reliability of the product,

e) The list of all excipients that should be indicated on the label and the manner in which they will be indicated.

The Ministry may issue supplementary guidelines or notifications relating to the enforcement of the

Regulation for conditions not indicated in this Regulation and where deemed necessary.

Penalty Provisions and Precautions
Article 20 – For those who fail to act in accordance with the provisions of this Regulation, Law No. 1262 on Pharmaceutical and Medicinal Preparations, dated 14/05/1928 and, according to the characteristics and nature of their acts, the provisions of Turkish Penal Code, with No. 5237, dated 26/09/2004 shall apply.

Furthermore, in case of detection of violation of the provisions of this Regulation, the measures and sanctions  envisaged  by the  Regulation  Regarding  the  Registration  of  Medicinal  Products  for  Human  Use published on the Official Gazette dated 19/01/2005, with No. 25705 shall apply.

Revoked Regulation
Article 21 – The Regulation Regarding the Packaging and Labeling of Pharmaceuticals for Human Use and  Medicinal Preparations published on the Official Gazette dated 24/4/1991, with No. 20851, has been revoked.

Temporary Article 1 – The packages and package inserts of the current medicinal products for human use which have been registered/permitted before the enforcement of this Regulation and of medicinal products for  human  use  for  which a  registration/permit  application has  been  made, shall  become  compliant  to  the provisions of this Regulation latest by 31/12/2007.

The applications to be made for the purpose of evaluating the package inserts encompassed by this Regulation shall be accepted by the Ministry as of the date this Regulation is published on the Official Gazette.

(The validity of this article has been extended to 01/07/2010 for original products and 31/12/2010 for generic products with the “Regulation Amending the Regulation Regarding the Packaging and Labeling of Medicinal Products for Human Use” published on the Official Gazette dated 30/05/2009, with No. 27243.)

Temporary Article 2 – Datamatrix shall be used on packaging of drugs for purposes of tracking and reimbursement. The term ‘karekod’ as used in this Regulation and other regulations issued in reference to this Regulation shall cover also the terms ‘cutout’ or ‘cutout or bar code’.