MANUFACTURING OPERATIONS HALALCERTIFIED FACILITY WHY 1 Kausar Ahmad

MANUFACTURING OPERATIONS HALAL-CERTIFIED FACILITY – WHY? 1 Kausar Ahmad Department of Pharmaceutical Technology Kulliyyah Of Pharmacy IIUM akausar@iium. edu. my PHM 4226 INDUSTRIAL PHARMACY

CONTENTS 2 �Halal and Haram in Islam A dietary choice? Halal issues Non-halal pharmaceuticals �Authorities & Halal Info �Regulatory requirements GMP Halal Pharmaceuticals based on MS 2424: 2012 Halal Certification PHM 4226 INDUSTRIAL PHARMACY

SHARIAH = ISLAMIC LAW 3 Preserve Faith Preserve Property Preserve Progeny PHM 4226 INDUSTRIAL PHARMACY Objectives of Shariah Preserve Life Preserve Intellect

On saving a LIFE The noble duty of healthcare professionals 4 Quran says: “Because of that We ordained for the Children of Israel that if anyone killed a person not in retaliation of murder, or (and) to spread mischief in the land it would be as if he killed all mankind, and if anyone saved a life, it would be as if he saved the life of all mankind. And indeed, there came to them Our Messengers with clear proofs, evidences, and signs, even then after that many of them continued to exceed the limits (e. g. by doing oppression unjustly and exceeding beyond the limits set by Allâh by committing the major sins) in the land!. []. ” (Q. al-Maidah, 5: 32) PHM 4226 INDUSTRIAL PHARMACY

CONSUME HALAL 5 �HALAL means LAWFUL. � Quran says: “O mankind! Eat of that which is lawful and wholesome in the earth, and follow not the footsteps of the devil. Lo! he is an open enemy for you. ” (Q. al-Baqarah, 2: 168) “O ye who believe! Eat of the good things wherewith We have provided you, and render thanks to Allah if it is (indeed) He Whom ye worship. ” (Q. al-Baqarah, 2: 172) “Eat of that which Allah hath bestowed on you as food lawful and good, and keep your duty to Allah in Whom ye are believers. ” (Q. al-Maidah, 5: 88) PHM 4226 INDUSTRIAL PHARMACY

AVOID HARAM 6 HARAM = FORBIDDEN PHM 4226 INDUSTRIAL PHARMACY

Quran says in 2: 219 7 “They ask you (O Muhammad SAW) concerning alcoholic drink and gambling. Say: "In them is a great sin, and (some) benefit for men, but the sin of them is greater than their benefit. " And they ask you what they ought to spend. Say: "That which is beyond your needs. " Thus Allâh makes clear to you His Laws in order that you may give thought. ” Q. al-Baqarah, 2: 219 PHM 4226 INDUSTRIAL PHARMACY

Quran says in 5: 3 8 “Forbidden to you (for food) are: Al Maytatah (the dead animals cattle beast not slaughtered), blood, the flesh of swine, and the meat of that which has been slaughtered as a sacrifice for others than Allâh, or has been slaughtered for idols, etc. , or on which Allâh's Name has not been mentioned while slaughtering, and that which has been killed by strangling, or by a violent blow, or by a headlong fall, or by the goring of horns and that which has been (partly) eaten by a wild animal unless you are able to slaughter it (before its death) and that which is sacrificed (slaughtered) on. An Nusub(stone altars). (Forbidden) also is to use arrows seeking luck or decision, (all) that is Fisqun (disobedience of Allâh and sin). This day, those who disbelieved have given up all hope of your religion, so fear them not, but fear Me. This day, I have perfected your religion for you, completed My Favour upon you, and have chosen for you Islâm as your religion. But as for him who is forced by severe hunger, with no inclination to sin (such can eat these above mentioned meats), then surely, Allâh is Oft Forgiving, Most Merciful. ” (Q. al-Maidah, 5: 3) PHM 4226 INDUSTRIAL PHARMACY

A DIETARY CHOICE? 9 Kosher Halal Vegetarian Vegan Gluten-free Lactose-free PHM 4226 INDUSTRIAL PHARMACY Sugar-free

HALAL ISSUES 10 Alcohol from fermentation Istihalah PHM 4226 INDUSTRIAL PHARMACY Gelatin API, VACCINES, EXCIPIENTS

HALAL ALTERNATIVES 11 Gelatin • Porcine • Unslaughtered bovine • Slaughtered cattle Alcohol • Fermentation • Synthetic PHM 4226 INDUSTRIAL PHARMACY Vaccines • Porcine • Bovine • Recombinant Source of API Excipients • Porcine • Unslaughtered bovine • Slaughtered bovine • Porcine • Unslaughtered bovine • Plant-based • Slaughtered bovine

PHM 4226 INDUSTRIAL PHARMACY 12

www. sustainableswineresources. com PHM 4226 INDUSTRIAL PHARMACY 13

+ Genetic Engineering 14 www. revivicor. com PHM 4226 INDUSTRIAL PHARMACY

EXAMPLES: PHARMACEUTICALS FROM PIGS 15 Origin Pharmaceutical Indication Route Product Ovary Relaxin Pregnancy Injection/ Suppository/ Transdermal Biolaxin (Sky Biohealth) Hypothalamus Somatostatin Endocrine Intravenous Aminopan (UCB Pharma) Nerve tissue Cephalins Liver function test Oral Livage (Aristo) Cartilage Chondroitin sulfate Arthritis Oral/ Intramuscular Chondrosulf (IBSA) Pituitary gland - anterior Somatotropin Growth hormone Injection Cryro-Tropin (Cryopharma) Oxytocin Birth/ Lactation Intravenous/ Spray Oxytocin (American Pharma) PHM 4226 INDUSTRIAL PHARMACY

NON-HALAL VACCINES – PORCINE GELATIN 16 Indication Product Manufacturer Gelatin per dose Rabies Rab. Avert Novartis Influenza Fluzone Aventis Pasteur 0. 05 % Japanese Encephalitis JE-Vax Aventis Pasteur 500 mcg Measle/Mums/Rubella MMR II Merck 14. 5 mg PHM 4226 INDUSTRIAL PHARMACY < 12 mg

VACCINES - MENINGITIS 17 Indication Product Origin Manufacturer Meningitis Menveo Bovine Novartis Meningitis Mencevax Bovine GSK Meningitis Menomune Porcine Sanofi PHM 4226 INDUSTRIAL PHARMACY

Alcohol rulings from www. e-fatwa. gov. my 18 1. Every wine contains alcohol. However not all alcohol are wine. Alcohol that is extracted from the winemaking process is ruled as prohibited (haram) and impure. 2. However, alcohol that is not produced through the winemaking process is not ruled as impure, but is prohibited (haram) from being consumed in its original form as it is a poison and can kill. 3. Light beverages processed/made not for the purpose of producing wine and containing alcohol below the level of 1% v/v are permissible to be consumed. 4. Whereas for light beverages made with the same intention and method of producing wine, regardless of whether their alcohol content is high or low or whether their alcohol content is distilled, their consumption is prohibited. 5. Food or beverages containing natural alcohol such as fruits, nuts, grains or their juices, or alcohol that incidentally forms during the production process of certain food or beverages is not considered impure and is permissible to be consumed. 6. Food or drinks with flavouring or colouring that contains alcohol for stabilisation purposes are permissible to be consumed provided that the alcohol is not produced from the winemaking process, the quantity of such alcohol in the final product is not intoxicating and the alcohol level does not exceed 0. 5%. 7. Medicines and perfumes containing alcohol as a solvent agent are not impure and are permissible provided such alcohol is not extracted from the winemaking process. PHM 4226 INDUSTRIAL PHARMACY

ABOUT ALCOHOL Commercial Name Beer Pilsner Stout Wine Sparkling wine/champagne Able wine Spirit/Hard Liquor Brandy Liqueurs (sweetened) Vodka Whisky Neutral Grain/Rectified Spirit Fortified wine Sherry Port Wine Absolute alcohol PHM 4226 INDUSTRIAL PHARMACY Origin 19 Malt Roasted malt or barley Grapes Grape Grain, potatoes, sugar Barley, corn, rye Barley or any grain Process Fermentation /distillation Various types of grapes with spirit added A mixture of wine and spirit Corn starch, Sugar cane Fermentation /distillation Petrochemical Synthesis Alcohol by volume (% v/v) 3 -6 5 -10 8 -12 9 -14 15 -25 40 80 95 -98 17 -22 16 -20 96 -98

Source of Edible Gelatin 20 HALAL NON-HALAL �Plant-based Pig Skin (80%) �Slaughtered From: Gelatin Manufacturers in Europe (2011) Gelatin Pig & Cattle Bones (5%) PHM 4226 INDUSTRIAL PHARMACY Cattle Hide Split (15%) bovine

Istihalah: Transformation & Conversion 21 Synthetic transformation RAW MATERIAL CONVERSION AGENT FINISHED PRODUCT Natural transformation http: //www. youtube. com/watch? feature=p layer_embedded&v=BRETz 2 F-he. Q PHM 4226 INDUSTRIAL PHARMACY

Types of Processes 22 Type Raw Process Final product Tanning Handbag material Physical Animal skin Physical changes only Chemical Wine Fermentation Vinegar Physical changes: odour Chemical structure different Physical/Chemical Pig skin Heating/ Gelatin Enzymatic Physical changes only Chemically similar THUS HARAM PHM 4226 INDUSTRIAL PHARMACY

AUTHORITIES & HALAL INFO 23 www. bpfk. gov. my www. halal. gov. my www. jakim. gov. my PHM 4226 INDUSTRIAL PHARMACY

General Guide 24 PHM 4226 INDUSTRIAL PHARMACY

HALAL INDEX 25 PHM 4226 INDUSTRIAL PHARMACY

INTERMISSION 26 PHM 4226 INDUSTRIAL PHARMACY

MANUFACTURING OPERATIONS HALAL STANDARD & REQUIREMENTS 27 Kausar Ahmad Department Of Pharmaceutical Technology Kulliyyah Of Pharmacy IIUM akausar@iium. edu. my PHM 4226 INDUSTRIAL PHARMACY

HALAL CERTIFICATION FOR PHARMACEUTICALS 28 • To cater for the needs of Muslims, and because of increasing awareness on the halal status of many medicines, there is great interest among Muslim healthcare professionals to produce halal pharmaceuticals. • Commencing January 1 st, 2013 - consent given by the Ministry of Health Malaysia to allow the use of the halal logo for over-the-counter medicines except for parenteral and veterinary products. • At the moment, ethical products (poison) such as mefenamic acid, amlodipine and gliclazide will not be given the halal status even if the raw materials used are halal-certified and the processes involved are free from non-halal elements. PHM 4226 INDUSTRIAL PHARMACY

Regulatory Requirements 29 NPCB JAKIM GMP MAL 123456 X PHM 4226 INDUSTRIAL PHARMACY Halal Logo

GMP & Drug-Related Regulations in Malaysia 30 PHM 4226 INDUSTRIAL PHARMACY

MALAYSIA - A SIGNEE OF PIC/S 31 • PIC/S is an abbreviation that refers to two international instruments: • Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme between countries and inspection authorities. • As trading becomes global, it is even more important for pharmaceutical products to be accepted worldwide as being safe irrespective of the country of origin. • Discussion: What is the impact of Trans-Pacific Partnership Agreement (TPPA) on halal pharmaceuticals? PHM 4226 INDUSTRIAL PHARMACY

OBJECTIVES OF PIC/S GMP GUIDELINES & ANNEXES 32 Harmonisation of GMP guidelines Mutual confidence in systems and products Uniform inspection systems Exchange of information Mutual recognition of inspections Training of inspectors PHM 4226 INDUSTRIAL PHARMACY

HALAL GUIDELINES 33 • The Malaysian Standard Halal Pharmaceuticals – General Guidelines MS 2424: 2012 was released by the Department of Standards Malaysia in 2010 • The guidelines would help manufacturer to know the requirements for obtaining the halal status of the products. • For a pharmaceutical product to be considered as halal • GMP-certified facility • ingredients must be halal • comply with T&C PHM 4226 INDUSTRIAL PHARMACY

MS 2424: 2012 HALAL PHARMACEUTICALS – GENERAL GUIDELINES 34 PHM 4226 INDUSTRIAL PHARMACY

MS 2424: 2012 - TERMS 35 � 3. 1 PHARMACEUTICALS Registered with DCA � 3. 2 HALAL PHARMACEUTICALS Absence of non-halal Absence of najs Safe for human use Equipment not contaminated with najs Absence of human parts and derivatives Separation of products from products that do not meet the halal requirements PHM 4226 INDUSTRIAL PHARMACY

MS 2424 - TERMS 36 � 3. 3 SHARIAH LAW As ordered by Allah Based on ASWJ � 3. 4 HALAL Permitted by Shariah law � 3. 5 NAJS Mughallazah, mutawassitah, mukhaffafah � 3. 6 COMPETENT AUTHORITY � 3. 7 MANUFACTURE � 3. 8 MANUFACTURING PREMISE � 3. 9 MATERIALS API, excipients & packaging materials PHM 4226 INDUSTRIAL PHARMACY

MS 2424: 2012 4 REQUIREMENTS, 4. 1 QUALITY MANAGEMENT 37 �Organisation shall ensure that halal pharmaceuticals are manufactured according to halal requirements. PHM 4226 INDUSTRIAL PHARMACY

MS 2424: 2012 4. 2 MANAGEMENT RESPONSIBILITY 38 �Implement Halal Assurance System. Facility is well-equipped to produce halal pharmaceutical goods Construction and design of production and processing line fulfilling the requirement of halal & GMP Should be implemented effectively and maintained as per GMP Production line dedicated for halal pharmaceuticals Normally, a facility that complies to GMP would be able to absorb all the basic manufacturing requirements Ensure halal commitment by all parties involved e. g. suppliers PHM 4226 INDUSTRIAL PHARMACY

MS 2424: 2012 4. 3 HALAL ASSURANCE SYSTEM 39 HALAL ASSURANCE PHM 4226 INDUSTRIAL PHARMACY

MS 2424: 2012 4. 4 FUNDAMENTALS FOR HALAL PHARMACEUTICALS IN GMP 40 Components in GMP Must comply to Good Manufacturing Practice (GMP) System & Documentation: Approved procedures & activities recorded Facility: Adequate space & services PHM 4226 INDUSTRIAL PHARMACY Personnel: Qualified & trained Materials: Halal Equipment: Dedicated for halal products Finished products: Not in contact with najs

MS 2424: 2012 4. 5 HALAL QUALITY CONTROL 41 Purchasing/ handling/ sourcing activities according to shariah Sampling & testing materials All materials used are halalcompliant Apparatus & equipment Chemicals & reagents PHM 4226 INDUSTRIAL PHARMACY Production materials Packaging materials

MS 2424: 2012 4. 5+ About SERTU 42 PRODUCT WHY? �Carried out when in contact with najis mughallazah � 100% natural refined clay. � - Collaboration Research with � � PHM 4226 INDUSTRIAL PHARMACY Halal Product Development Institute, Universiti Putra Malaysia (HPRI, ). - Certified by SIRIM. - Received professional advice and views from Syariah Review Panel, JAKIM and recommended as a product for samak/sertu purposes. - Approved by JAKIM, Malaysia and Ministry of Health of Republic Indonesia. - Registered under Ministry of Finance Malaysia.

MS 2424: 2012 4. 6 PERSONNEL AND RESPONSIBILITY 43 �Sufficient qualified personnel to maintain Halal Assurance System �Halal Committee: Leader: Muslim Members: 2/3 Muslim Must include purchasing personnel PHM 4226 INDUSTRIAL PHARMACY

MS 2424: 2012 4. 6+ HALAL COMMITTEE – JOB SCOPE 44 � Establish a halal committee. � Review and endorse raw material for ‘halalness’. � Conduct training on halal principles. � Conduct internal halal audit. � Assure that all equipment and tools are dedicated to manufacturing of halal products. � Assure that all documentation shall have all the halal certificates and related information. PHM 4226 INDUSTRIAL PHARMACY

MS 2424: 2012 4. 7 TRAINING 45 • Ensure sufficient number of qualified personnel with the capability of maintaining the Halal Assurance System • this can be achieved by continuous implementation of On-Job-Training (OJT). PHM 4226 INDUSTRIAL PHARMACY

MS 2424: 2012 4. 8 PERSONAL HYGIENE 46 �Must comply PIC/S GMP Guidelines & Annexes �Q: HOW TO ASSURE PERSONAL HYGIENE? PHM 4226 INDUSTRIAL PHARMACY

MS 2424: 2012 4. 9 PREMISE AND EQUIPMENT 47 • Layout and design of the premise must be in accordance with GMP or PIC/s layout design requirement. • Premise must be well separated by distance and other means from any non-halal animal activity area to prevent cross contamination through air, water, personnel or sewage. • Design and construction of equipment used for halal products must be in accordance with shariah requirements as well as GMP requirements. • Premise and equipment must be dedicated for the manufacturing of halal pharmaceuticals. � Equipment MUST NOT be in contact with or contaminated with najs. Otherwise, equipment must go through cleansing process sertu PHM 4226 INDUSTRIAL PHARMACY

MS 2424: 2012 4. 10 PRODUCTION AND STORAGE AREA 48 • Logistics: Halal pharmaceuticals are physically segregated during handling and storage from non-halal products. • The production and storage area of pharmaceutical product shall be provided with dedicated and self-sufficient facility so that it can minimise the chance of contamination of product or ingredients to become non-halal. • If the halal pharmaceutical is in need of animal facility, then the animal handling area must be isolated from other manufacturing areas; with different entrance for animal access and different air handling unit. • The latest technology involving production processes, equipment or utilities can be obtained through the website managed by the International Society for Pharmaceutical Engineering, www. ispe. org. PHM 4226 INDUSTRIAL PHARMACY

MS 2424: 2012 4. 11 QUALITY CONTROL AREAS 49 • The quality control system must comply with halal requirements as well as with GMP requirements. • The procurement of chemical, reagents or other ancillary equipment required for sampling and testing must not be made using materials that are not halal or dubious. • Precautions must be taken to prevent contamination that may affect the halal nature of product during conducting quality control activities in production area. • Can investigate presence of porcine PHM 4226 INDUSTRIAL PHARMACY

MS 2424: 2012 4. 11+ HALAL TRACEABILITY SYSTEM 50 WHY? �If suspect possibility of porcine contamination /adulteration PHM 4226 INDUSTRIAL PHARMACY PORCINE DNA TEST KIT �detect existence of porcine DNA in food and non-food products �using portable Polymerase Chain Reaction (PCR). �PCR machine performs sample digestion/DNA extraction, PCR reaction and detection

MS 2424: 2012 4. 11+ PORCINE DNA TEST KIT 51 PHM 4226 INDUSTRIAL PHARMACY

MS 2424: 2012 4. 12 ANCILLARY AREAS 52 • The halal facility may also include • resource centre for Islamic knowledge and values • designated praying areas for male and female employees • training facilities PHM 4226 INDUSTRIAL PHARMACY

MS 2424: 2012 4. 13 DOCUMENTATION 53 � It is important to make sure that the work processes as documented in the SOP and related documents have included the halal aspect of the manufacturing process. Halal certificates Product data sheet BMR SOP PHM 4226 INDUSTRIAL PHARMACY

MS 2424: 2012 4. 14 PRODUCTION - HALAL PRODUCTION ACTIVITIES 54 PHM 4226 INDUSTRIAL PHARMACY

MS 242: 2012 4. 15 RAW MATERIALS AND PACKAGING MATERIALS 55 • All materials involved in the manufacturing of halal pharmaceutical product starting from raw material to packaging material must be halal. Free from any parts or products originating from non-halal animals or animals that are not slaughtered, or human. Non-poisonous, non-intoxicating and non-hazardous to health. � This can be confirmed by obtaining a halal certificate. • Otherwise, the halal committee is at task to discern the permissibility of the material. • The materials may be synthetic or derived from natural source that is in accordance with shariah. PHM 4226 INDUSTRIAL PHARMACY

MS 242: 2012 4. 16 PACKAGING MATERIALS 56 �Consumables & non- consumables must be from halal origin. �Design and name must not contravene shariah law. PHM 4226 INDUSTRIAL PHARMACY

MS 2424: 2012 5 COMPLIANCE - HALAL AUDIT 57 A halal audit will only be conducted after a product has been registered with NPCB. Halal audit will be conducted by representatives from the certified body on a scheduled or a non-scheduled basis (compliance). Upon completion and with satisfactory outcome, the product will be issued with a halal certificate. A unique number will be given and the manufacturer may use the halal certification mark or logo, with the number indicated right below it. PHM 4226 INDUSTRIAL PHARMACY

MS 2424: 2012 6 HALAL CERTIFICATES - HALAL CERTIFICATION BODIES 58 • Jabatan Kemajuan Islam Malaysia, JAKIM, is the body entrusted with the issuance of the halal certificate. • JAKIM can get the involvement of the religious bodies in the respective state to handle the request for halal certification. • • In the state of Pahang, representatives from Jabatan Agama Islam Pahang (JAIP) may audit product in the Notification category such as hand sanitisers. Due to worldwide distribution of halal products, JAKIM has endorsed selected foreign halal approving bodies that provide halal certification e. g. Australian Federation of Islamic Councils Inc. without doubt. PHM 4226 INDUSTRIAL PHARMACY

MS 2424: 2012 7 HALAL CERTIFICATION MARK - HALAL LOGO 59 Reference/Certificate number for the halal product Guideline used for the manufacturing process The approved halal logo issued by JAKIM with the manufacturing standard used and the certificate number to be positioned beneath the logo PHM 4226 INDUSTRIAL PHARMACY

HALAL PHARMACEUTICALS IN MALAYSIA 60 CCM PHM 4226 INDUSTRIAL PHARMACY IKOP

CONCLUSION 61 Halal pharmaceuticals is a religious requirement√ Halal certification for OTC√ Halal calls for INTEGRITY√ PHM 4226 INDUSTRIAL PHARMACY

Text book: Manufacturing of Halal Pharmaceuticals 62 PHM 4226 INDUSTRIAL PHARMACY

REFERENCES 63 Abdul Halim Ihsan (2011). The Halal Index Volume 1: Pig-based Pharmaceuticals. Kuala Lumpur: Phytorex Press. Abdul Halim Ihsan (2013). Adakah ubat-ubatan anda halal? Kuala Lumpur: Halim Ihsan Publications. Department of Standards Malaysia (2012). Malaysian Standard MS 2424: 2012 Halal Pharmaceuticals – General Guidelines. Kuala Lumpur: Standards Kausar Ahmad (2015). Manufacturing of Halal Pharmaceuticals. Kuala Lumpur: IIUM Press. Mohammad Aizat Jamaludin, Mohd Anuar Ramli, Dzulkifly Mat Hashim and Suhaimi Ab Rahman (2012). Fiqh Istihalah: Integration of Science and Islamic Law. Revelation and Science Vol. 02, No. 02 (1434 H/2012) 49 -55. Pharmaceutical Inspection Convention & Pharmaceutical Inspection Co-Operation Scheme (PIC/S) (2009). Guide to good manufacturing practice for medicinal products part I (PE 009 -8 -Part I). Geneva: PIC/S. World Health Organisation (1992). Good Manufacturing Practices for Pharmaceutical Products. Technical Report Series No. 823. Geneva: WHO. Yusuf al-Qaradawi (1994). The Lawful and the Prohibited in Islam. Kuala Lumpur: Islamic Book Trust PHM 4226 INDUSTRIAL PHARMACY