Guidance for Classifying the Prescription & Distribution Status Of

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Version 1.0 Draft [Not for implementation and published for comment purposes]

Date of publication 16/11/2017

Guidance for Classifying the Prescription & Distribution Status of Medicinal Products

Version 1.0

Drug Sector Saudi Food & Drug Authority

Please review and send your comments or suggestions within 90 days of publication to: [email protected]

Please visit SFDA’s website at http://www.sfda.gov.sa/en/drug/drug_reg/Pages/default.aspx for the latest update

Drug Sector

Vision and Mission

Vision

To be the leading regional Drug Regulatory Authority for pharmaceuticals and cosmetic products, with professional excellence and services that contribute to the protection and advancement of public health in the Kingdom of Saudi Arabia. الرؤية

أن يكون قطاع ادلواء رائدًا اقلميي ًا يف الرقابة عىل ا لدوية ومس تحرضات التجميل، ويقدم خدماته مبهنية م متزية تسهم يف حامية وتعزيز الصحة يف اململكة العربية السعودية.

Mission

Protecting public health by ensuring safety, quality, efficacy and accessibility of human, veterinary drugs and biological products, and safety of cosmetics, through administration of a national regulatory system which is consistent with international best practice. Through our mission, we also provide accurate and scientific-based information to the public and healthcare professionals. الرساةل

حامية الصحة العامة من خالل ضامن أمان وجودة وفعالية وتوفر ا لدوية البرشية والبيطرية واملنتجات احليوية وسالمة مواد التجميل عرب تطبيق نظام وطين للرقابة متوافق مع أفضل املامرسات ادلولية وتقدمي املعلومات ادلوائية املبن ية عىل أسس علمية للعامة واملهنيني الصحيني.

Document Control

Version Date Department Comments 1.0 16/11/2017 National Drug and Poison Draft for comments Information Center

Contents Introduction: ...... 6 Scope: ...... 6 Definitions: ...... 6 Part I: Criteria and Requirements for Classifying the prescription Status of Medicinal Products .. 7 1. Criteria for classification as Prescription Only Medicinal Product (POM) ...... 7 2. Criteria for Classification as Over-The-Counter (OTC) Product: ...... 10 3. Requirements: ...... 12 PART II: Criteria for Classifying the Distribution Status of Medicinal Products ...... 13 References: ...... 16

Introduction: This guidance addresses the criteria to be followed by SFDA when determining the prescription and distribution status of medicinal products.

This guidance is classified into two main parts:

- PART I: Criteria and requirements for classifying the prescription status of medicinal products in Saudi Arabia. - PART II: Criteria for setting the distribution status of medicinal products in Saudi Arabia.

Scope: This guidance is applicable to SFDA registered or under-registration medicinal products intended for human use in Saudi Arabia.

Definitions: - Controlled Medicinal Product: a prescription only medicine that is subject to Law of Narcotics Control in Saudi Arabia. - Distribution Status: places where patients / consumers can purchase or gain access to medicinal products (i.e. pharmacies, hospitals). - Hospital: includes governmental hospitals pharmacies, private hospitals inpatient pharmacies, and primary care clinics. - Over-The-Counter (OTC) Product: a medicinal product subject to SFDA authority that could be obtained by patients in Saudi Arabia without a physician’s prescription. - Prescription or legal Status: the conditions and restrictions under which the medicinal product should be made available to patients. - Prescription Only Medicine (POM): a medicinal product that is subject to SFDA authority and that is available to patients in Saudi Arabia only based on a licensed physician’s prescription in Saudi Arabia. - PIL: Patient Information Leaflet - SFDA: Saudi Food and Drug Authority. - SPC: Summary of Product Characteristics

Part I: Criteria and requirements for classifying the prescription status of medicinal products

1. Criteria for classification as Prescription Only Medicinal Product (POM) 1.1.Safety: Medicinal products shall be subject to medical prescription when the supervision by a healthcare practitioner is necessary for the diagnosis, treatment, and prevention or monitoring of a disease with respect to the appropriate choice of a medicinal product. In addition, medicinal products shall be subject to medical prescription when they are likely to present a danger directly or indirectly, even when used correctly, if utilized without medical supervision. In considering whether this criterion applies, the following factors should be addressed: 1.1.1 The drug is used in the treatment of a serious disease not easily diagnosed by the public. In these situations, the involvement of a practitioner in the diagnosis, treatment and monitoring of the disease, including selecting and monitoring the use of the drug can help decrease the chances of harm occurring, as well as increase the benefits. Example - Human patients with hypothyroidism [low thyroid function]. 1.1.2 The use of the drug may mask other diseases, and may result in any of the following:  A lack of timely diagnosis and treatment  A significant worsening of the underlying disease; or  Otherwise putting at risk the chance of more successful therapy, the drug will likely be given prescription status. 1.1.3 The use of the drug requires complex or individualized instructions:  There are two main reasons why individualized instructions may be necessary: when the use of a drug needs to be tailored to a patient’s specific

circumstances or when the drug information cannot be easily understood by the general population.

1.1.4 The drug has a narrow margin of safety.  For some drugs, the difference between a therapeutic (helpful) dose, and a toxic one, is very small, so it is critical that the patient receive precisely the right amount of drug to prevent serious consequences. 1.1.5 At normal therapeutic dosage levels, the drug has potential or is known to cause serious adverse reactions or serious interactions with food or other drugs.  A drug would be typically authorized as a prescription drug if when used at a normal dosage level, it can cause serious adverse reactions or can result in serious interactions with food or other drugs. Practitioner involvement is required for communicating and managing the risks to patients. o Example: Warfarin is a drug used to prevent clots in the blood. If human patients eat too much of certain foods (e.g., dark leafy green vegetables) while taking this drug, this can lead to an increased potential for blood clots. 1.1.6 The use of the drug may lead to indirect danger to human health, even when used correctly, if used without medical supervision.  A medicinal product would increase the risk of resistance to the product, in particular in the general population, to such an extent that the usefulness of any medicinal product is likely to be compromised e.g. Antibiotic. 1.1.7 The drug has frequent incorrect use which could lead to direct or indirect danger to human health. 1.1.8 Practitioner expertise is necessary to administer the drug or oversee the drug’s administration, as with the following classes:  Parenteral Product  Enemas  Irrigations used wholly or mainly for wounds, bladder, vagina or rectum

1.2.Limited Marketing Experience: Medicinal products shall be subject to medical prescription when they contain substances or preparations where the activity and/or side-effects require further investigation. In considering whether this criterion applies, the following factors should be addressed: 1.2.1 Recent authorization/limited marketing experience of the drug.  Further investigation may be necessary when a medicinal product has only recently been granted a marketing authorisation or because of limited experience/use of the product e.g. Orphan drugs.  Even if clinical trial data are extensive and reassuring, it is important to have post-marketing experience in the general population, that is evidence of patients, which may be imposed by the design of clinical trials e.g. the elderly, children, certain racial or phenotypic groups and those having certain medical conditions. Products which have different safety or efficacy profiles in different racial or phenotypic groups may need special warnings. 1.2.2 New strength, dose, route of administration, indication, new age group or combination of substances.  A drug may have been on the market but is now being proposed for sale with a change to its conditions of use (e.g., a new use, strength, dose, species, age group, or route of administration). In some cases, there may be gaps in the information regarding the long-term consequences associated with the new use. In these cases, prescription status would help to ensure practitioner oversight. 1.3.Risk of Abuse/Dependence: Medicinal products shall be subject to controlled medical prescription when they contain substances that may cause any type of abuse/dependence. Refer to the Narcotics Control Law of Saudi Arabia to identify list of controlled substances.

2. Criteria for Classification as Over-The-Counter (OTC) Product: Medicinal products can be classified as OTC products when they are likely considered safe to be used by the public without the need of supervision by a healthcare practitioner. In considering whether this criterion applies, the following factors should be addressed: 2.1. Supervision by a healthcare practitioner is not necessary: 2.1.1. Diseases or symptoms can be easily and correctly diagnosed, treated and monitored by the public with respect of the drug recommended for use:  The risks associated with a misdiagnosis of symptoms, and/or a delay in using the appropriate treatment or use of sub-optimal treatment should be addressed. o A cautionary statements on the product label could be included, e.g. after a certain period of time, if symptoms /signs continue in the patient, a practitioner should be consulted. (Refer to the GCC Guidance for Presenting the SPC, PIL and Labeling Information)  Any collateral measures might be needed for effective use of the treatment, should be usable without practitioner intervention. 2.1.2. The utilization, administration and/or monitoring of the medicinal product should not require complex or individualized instructions:  The selection of proper medicinal product and dosing should be easily and correctly achieved by the patient  Product information can be easily understood and followed by the public  Self-administration must be done without healthcare provider’s supervision  Benefit can be achieved when utilized without a guidance of health care provider  Monitoring parameters for the effective/safe use of the medicinal product must be assessed by the patient without practitioner’s intervention

2.2. The Medicinal Product should have an adequate margin of safety 2.2.1. The product should not lead to direct or indirect danger when used without medical supervision  Examples on direct danger may include: o adverse reactions that are important because of their seriousness, severity or frequency or because the reaction is one for which there is no suitable preventative action such as the exclusion of a clearly identifiable risk group. o serious danger arising from drug interactions with food or other drugs  Examples on indirect danger may include: o When symptomatic treatment might mask an underlying condition requiring medical attention. o Increased risk of development of bacterial resistance in the community as a result of the wide use of antibiotics without medical supervision. 2.2.2. The medicinal product should not poses a Narrow Therapeutic Index 2.2.3. The medicinal product must not have potential to produce serious adverse reactions in particular subpopulation (e.g. children, pregnant and/or elderly). 2.2.4. The consequences of misuse of the product are minor:  The risk to health is small if the consumer uses the product when it is not indicated, exceeds the recommended dose or recommended length of treatment, or fails to read the contraindications or warnings  The intentional and unintentional misuse or accidental overdose should be addressed 2.2.5. The use of the product does not lead to abuse / dependence. 2.3. The medicinal product should have adequate market experience.

3. Requirements: The classification of the Legal Status of medicinal products takes place following the full assessment of products undergoing registration by the SFDA (Refer to the GCC Data requirements for Human Drugs).

In addition to SFDA data requirements, the followings are special considerations for products classified as OTC Products: 3.1. Product Information:  The PIL should provide information on appropriately describe the use of the product and the circumstances when referral for medical advice is appropriate.  Contraindications and warnings, such as advice limiting duration of treatment or the need to consult a doctor in certain situations, should be provided as appropriate.  Refer to The GCC Guidance for Presenting SPC, PIL, and Labelling Information. 3.2. Pack size and container:  The pack size should be decided in relation to the intended length of the treatment. Restricting the availability of a medicinal product to a small pack size is a possible safeguard against misuse, particularly overdose, or a delay in seeking medical attention.  Container closure system should be designed to provide child resistance closure. For more information, refer to the Guidelines on Container Closure Systems.

PART II: Criteria for Classifying the Distribution Status of Medicinal Products The distribution status of medicinal products is classified into either:  Hospitals  Pharmacies  General Sales List

Based on the following criteria:

1. Legal Status: The Legal Status of a Medicinal Product will define its Distribution Status based on the following: 1.1. POM: Depends on dosage form and route of administration (See the table below). 1.2. OTC: OTC products are distributed in pharmacies. 1.3. Herbal / Health products: pharmacies and supplement stores.

Table: Definition of Distribution Status of POM Medicinal Products based on Dosage Form / Route of Administration

Dosage Form / ROA Distribution Status Intravenous Hospitals Exceptions: - IV Normal Saline when used with nebulization for asthmatic patients is eligible to be distributed in pharmacies. Intramuscular Hospitals Exceptions: - Antibiotics: (Amoxicillin, Ampicillin, Augmentin, Ceftriaxone, Cefuroxime) Intrathecal Hospitals Intra-arterial Hospitals Subcutaneous Hospitals Exceptions: - Insulin: Pharmacies Intravitreal Hospitals Epidural Hospitals

Oral: Solid & Liquid Pharmacies Exceptions: - Controlled: Only specified retail pharmacies are eligible to handle controlled medicinal products. Refer to SFDA website for list of eligible pharmacies. - Pregabalin: Hospitals - Medicinal Products which require certain/specialist supervision (ex. Chemotherapy) Inhaled Pharmacies Exceptions: - Inhaled anesthetics: Hospitals Topical Pharmacies Rectal Pharmacies - Suppositories Exception:

- Controlled (ex. Diazepam): Hospitals Hospitals - Enemas Pessaries Pharmacies

Exception:

- Misoprostol: Hospitals Nasal Drops / Spray Pharmacies Eye Drops Pharmacies Transdermal Patch Pharmacies Exception: - Controlled (ex. Fentanyl): Hospitals Transdermal Implant Hospitals Intrauterine Device Hospitals

2. SFDA Circulars / Memos: SFDA may issue circulars or memos specifying or modifying the distribution status of marketed medicinal products in Saudi Arabia based on safety updates.

3. General Sales List (GSL): Based on the decision of the Registration Committee of Pharmaceutical Companies number 31/SFDA/718/17 and the decision of the Registration Committee of Herbal and Health Products number 1431/SFDA-357/6, retail stores equipped with adequate storage conditions for pharmaceutical products are allowed to sell the following products. Refer to the Pharmaceutical Products Allowed to be Sold in Food Retail Stores.

References:

1- GUIDANCE DOCUMENT: Determining Prescription Status for Human and Veterinary Drugs, Health Canada, December 2013. 2- Regulation of non-prescription drug, FDA. 3- Guidance for Industry Labeling OTC Human Drug Products , FDA, December 2008. 4- Medicines for Human Use: POM, P, GSL & General Pharmacy Regulations, Northern Ireland, 2010 Edition. 5- GUIDANCE DOCUMENT, Labelling of Pharmaceutical Drugs for Human Use, health Canada , June 2015. 6- Narcotic & Controlled (Psychotropic) Drugs Policy and Procedure. Ministry of Health, Saudi Arabia.