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It applies to many areas including aspects of automotive products, fisheries, agriculture, aviation and food and indeed to anything where internal barriers to trade may occur and a single market is desirable. However, certain commodities are subject to strict regulation under EU legislation and among these are many types of chemical speciality. These are frequently regulated under EU directives, regulations and decisions by national competent authorities and by EU agencies, as shown below in Table 1. Regulation of Pharmaceuticals Pharmaceuticals, including veterinary medicinal products, were for a long time regulated in the UK under the Medicines Act , and by Statutory Instruments made under the Act.

Following the major revision of the veterinary pharmaceutical legislation in , the use of the Medicines Act was all but abandoned except for some UK-specific sections. Instead, it has been replaced by the Veterinary Medicines Regulations. The latest incarnation of these are The Veterinary Medicines Regulations This applied to human and veterinary medicinal products and it introduced the concept of the marketing authorisation MA subject to the criteria of safety, quality and efficacy.

This legislation required that no pharmacologically active substance could be used in veterinary medicinal products intended for use in food animals unless MRLs had been established or MRLs were considered unnecessary and the legislation was applied retrospectively to all existing pharmacologically active substances. In , this changed again after a review of the veterinary and human pharmaceutical legislation, as indicated earlier. Under the amended Directive, a number of changes were introduced, including the introduction of the decentralised procedure, while a coordination group previously set up under a voluntary basis to try and resolve scientific disputes with the mutual recognition procedure was given statutory backing as the Coordination Group for Mutual Recognition and Decentralised Procedures veterinary CMDv , and, as its name suggests, it now attempts to resolve issues not only for the mutual recognition procedure, but also for the decentralised procedure, a procedure broadly similar to that of mutual recognition, but which involves simultaneous submission to all countries, rather than an initial submission in one followed by subsequent submissions to the other.

Both the new amending directive and the new regulation substantively upgraded the requirements for pharmacovigilance, while the CVMP became the Committee for Medicinal Products for Veterinary Use. The UK has representatives on most of these groups. It has a number of functions, including the development of regulatory strategy and training and benchmarking regulatory agencies. One of its most critical roles is the provision of the statutory Coordination Groups, the CMDv mentioned earlier, and the corresponding group for human medicinal products, the CMDh, both of which work to resolve issues encountered in mutual recognition and decentralised procedures in their corresponding sectors.

The UK frequently acts as rapporteur or co-rapporteur for centralised procedures and for MRL applications, and as reference member state for mutual recognition and decentralised procedures. It also takes on responsibilities for formulating guidelines 18 International Animal Health Journal. Marketing Authorisations For veterinary medicinal products, a high proportion of marketing authorisations MAs are national MAs granted prior to the introduction of the European procedures. In the UK, these were originally issued as product licences. However, there are now a large number of MAs issued under the mutual recognition or decentralised procedures which of course are also national MAs , and a small number of national authorisations granted since the inception of the new procedures, but which, for a variety of reasons e.

Over veterinary medicinal products have been authorised through the centralised procedure although several of these have since been withdrawn by the MAH. Others have been subject to a referral procedure and so specific aspects of data have been subject to a CVMP opinion and a Commission Decision, usually with subsequent amendments to the SPC and product literature.

If the UK withdrew from the EU and the EEA, all of the national marketing authorisations would remain valid, including those authorised through mutual recognition or the decentralised procedures, although the UK would no longer need to maintain harmonised aspects of the summary of product characteristics SPC or labelling, or abide by any restrictions imposed as a result of the procedures.

However, the UK could presumably opt to issue a UK MA for existing centralised procedure products or even for future ones, or at least implement a fast-track procedure for the latter, without further assessment. If it failed to do this, and determined UK-specific indications, contraindications, posology and, in the case of food producing animals, withdrawal periods, then the MAH could face barriers to Volume 1 Issue 2. The issue of withdrawal periods is extremely important in this respect. A withdrawal period sometime called a withholding period is the time that must elapse between drug administration and slaughter for human consumption, or before produce such as eggs, milk and honey can be collected for human consumption.

They are based on the time taken for depletion of drug residues to a safe concentration, which is almost exclusively the EU MRL see next section. If the UK were to establish its own MRL values, or if it adopted EU MRLs but calculated withdrawal periods different from those established in EU countries for the same product, or even if it permitted the use of drugs prohibited under EU legislation, then it would create potential barriers to trade in animal produce with the EU and EEA states.

These issues may appear academic, but it is important to learn lessons from the past, before the time of introduction of the EU procedures. Then it was entirely possible for a product to be authorised for dogs and cats in one country, for countries which regarded the horse as a non-food animal such as the UK , for dogs, cats and horses, while other countries may have these species alongside various food animals, including minor food species such as rabbits, ducks and goats. In short, almost any combination could, and did, exist across the EU for any given product.

Where products were indicated for use in food species, in addition to the discrepancies www. The MRL procedure is similar in many aspects to that of the centralised procedure and a rapporteur and co-rapporteur are appointed by the CVMP to handle the assessment of data and to prepare assessment reports. Alternatively, they may be International Animal Health Journal Table 2 prohibited substances of the Annex contains a small number of drugs or groups of drugs whose use in food animals is not permitted on consumer safety grounds.

However, as described earlier, this would raise potential problems for trade in food of animal origin with the Community, possibly similar to those which have arisen because of the legal use of anabolic and other production-enhancing drugs in the United States. This Directive requires member states to examine food of animal origin for the presence of residues of certain classes of drugs including those with an anabolic effect, antimicrobial substances, anthelmintics, sedatives and non-steroidal anti-inflammatory drugs, as well as other substances and environmental contaminants such as chemical elements e.

The Directive requires member states to draw up a national residues monitoring plan, which needs to comply with its Annex IV which establishes the sampling frequencies, and the types of animal and commodities to be tested. The Directive required the submission of an initial surveillance plan, followed by subsequent annual plans to be submitted to the Commission for scrutiny and approval. It is supplemented by a NonStatutory Surveillance Scheme which looks for similar violations of residues, mainly in imported foods.

In effect, the UK would become a third country under the terms of the Directive, and would still need to submit a surveillance plan and conduct residues surveillance in compliance with Article 29, if it wished to export its produce to the EU. In fact, this would apply equally to QPPVs working in pharmacovigilance of human medicinal products. This would not result in major consequences for many companies which already have offices and operations in these countries, but it could result in logistical problems for those without these facilities.

The UK would then be regarded as a third country, and UK companies or subsidiaries marketing products within the EU would be subjected to the requirements for third countries as set out in paragraph 2. Moreover, the manufacturer must hold a manufacturing authorisation ManA. ManA applications are made to the VMD except for those manufacturers which produce veterinary and human medicinal products where applications are made to the MHRA. The manufacturer must appoint at least one Qualified Person and the QP has statutory duties, especially for release of product for sale and use.

One of the requirements under the Directive is that the Volume 1 Issue 2. However, the manufacturing facilities would need to comply with the requirements of EU legislation, would need to hold a ManA, would need to be GMP-compliant and would be subject to inspection from EU competent authorities.

Rather, it is intended to highlight some of the key consequences. However, if the UK withdrew from the EU and the EEA, substantive changes or adaptations would be needed in a number of areas, as described above. Many of these changes, with the obvious exception of MRLs, would also apply to human medicinal products. However, it would also lose wider influence as a result of its loss of membership of the European Commission and the Council of Ministers. It must be emphasised that there has been no suggestion that the UK would not remain as an EEA country.

Moreover, to avoid some of the obligations that the UK regards as onerous, then leaving the EEA would seem a logical step. Although EFTA www. References 1. Teasdale and T. The Penguin Companion to European Union, 4th ed.

28 November 2005

Brixit looms. The Economist, June 21, A Blueprint for Britain: Openness not Isolation. Institute of Economic Affairs, London, Lisman and C. Brookwood Medical Publications, London, Veterinary pharmacovigilance in the European Union in K. Woodward ed. Veterinary Pharmacovigilance. Adverse Reactions to Veterinary Medicinal Products. Wiley-Blackwell, Chichester, , pp.

Regulation of veterinary medicines.

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Consumer safety — maximum residue limits. Regulatory Rapporteur, , Vol. Veterinary Medicines Directorate. Veterinary Medicines Guidance Note No Manufacturing Authorisations, July Available from www. Dr Kevin Woodward is an independent consultant in veterinary regulatory affairs. His areas of expertise include toxicology, residues, user safety and pharmacovigilance. Kevin has authored or edited three books and published over scientific articles and book chapters. He is a qualified toxicologist and a Fellow of the Royal College of Pathologists. E-mail: knw knwanimalhealthconsulting.

The Commission published their proposals for the updating of the veterinary medicines and feed medications legislation in Europe in September, five years after starting the review process. The regulatory bodies, industry and veterinarians have started their analysis and the first reactions are emerging. Stakeholders quickly took all of the available remaining places at the TOPRA veterinary symposium in Brussels in October to hear from the Commission, exchange views and ask questions.

There is universal welcome of the recognition that the veterinary medicines sector is very different from the human, and the formal separation of their legal frameworks is a major step forward. Member states will lose the flexibility that allowed national nuances in implementation, and marketing authorisation holders and applicants will have a more predictable, harmonised regulatory environment, as they wished. This satisfaction is tempered by the realisation that the proposals have left much unsaid or undefined. I counted 17 different references to implementing acts, directed inter alia at fees, labelling, variations and particularly antimicrobial resistance.

Once the Regulations are final, how far and how significantly will we be able to influence the important details in these Acts? IFAH Europe has been quick to point out that to reach the proportional administrative cost of human medicines, the reduction would need to be doubled. The major administrative burdens were identified, 22 International Animal Health Journal. National languages will no longer be required on marketed packs, but the member states will be able to opt for other languages.

Industry has long called for such changes to reduce the cost of placing products on the smaller markets, and the changes should further facilitate multi-country packaging. However, the extensive work by CMDv and industry task forces in recent years, reducing to a minimum the packaging constraints within current rules, have not really had any significant impact on availability in smaller markets so far.

Twenty five percent of the identified burden was around variations. What will be included in the list? As an example, for immunologicals it is difficult to see how most of the changes related to manufacturing or quality could be assumed to be without effect on safety or efficacy without an assessment. The changes variations are one of the areas where the details will be through implementing acts, and one where all stakeholders will be paying close attention.

The relaxation of pre-assessment is counterbalanced by an emphasis on verifying compliance by inspection and this will simply move the burden. Competent authorities will be required to inspect, on a risk basis, at all stages from manufacture and application to supply, and the Commission will audit this process. The Commission has taken the view that a single expensive and resourcedemanding pan-European process would disadvantage SMEs, so the national route plus mutual recognition for Volume 1 Issue 2. The decentralised procedure is available for access to a limited number of member states and the centralised procedure for the innovative and pan-European products.

Although the Commission claims that simplification will remove some of the barriers to a true single market, on the face of it this is not addressing its objective of reducing the bureaucratic burden and a single market still seems some way distant, to me at least. The framework for dossier content, application, validation and assessment timetables are common across the procedures, and the Commission has stressed that there will be only one assessment for a new authorisation or for a change, either at a national, pan-national or European level, with decision by a simple majority in the MRP or DCP.

Further re-assessment for geographical extension is not allowed, so the initial assessment in an MRP or DCP with a few concerned member states will be followed by a purely administrative rollout procedure to others. It would seem that there are battles of principle to be fought over the coming months, and the outcome will be fundamental to the shape of the regulatory landscape.

The centralised procedure remains the prescribed route for innovative products including new actives, biotechnologies and growth enhancers although this list may be changed though a delegated act but it has been opened to all who wish to use it and can afford the higher fees and associated costs inherent in a pan-European authorisation. The new CP will even allow generics of a nationally authorised product provided there is no other authorisation in the Community. Good manufacturing practice remains for veterinary medicinal products and active ingredients as expected, but its scope appears to have been extended to cover intermediate products and excipients.

If confirmed, is this extension of manufacturing requirements really necessary? The Commission has indicated that pharmacovigilance www. More reliance will be placed on electronic systems and a dedicated Europe-wide pharmacovigilance database will be established into which all adverse events in the Union will be recorded and shared. The database will have variable access for competent authorities, marketing authorisation holders and the public.

This will make surveillance at the Union level practicable, and should impose a consistent approach across the countries and authorisation routes. There will be a pharmacovigilance Masterfile linked to the marketing authorisation holder, rather than the product, and the periodic safety update report will be abandoned. Instead, there will be a requirement on authorisation holders and competent authorities alike to record all adverse events — human or animal, serious or mild — within 30 days into the database.

Surveillance by competent authorities will focus on signal detection, and the Regulation provides various mechanisms to allow and promote sharing of responsibilities between authorities and targeting of products or groups of products of concern. Competent authorities will be required to promote adverse event reporting by veterinarians and owners. All sectors of industry have consistently argued that the great majority of the estimated 30, existing marketing authorisations must be brought to wider access across the member states in an administrative process that preserves the existing indications and target species, while acknowledging that some products may require assessment.

The CVMP, however, must identify the groups of products where a re-assessment should, in their view, be carried out. The reassessment will then be mandated by further implementing acts by the Commission. Will the competent authorities easily accept harmonising to the shortest withdrawal period without reassessment? The global marketing authorisation principle is maintained and protection for listed species — cattle, sheep, pigs, chickens, dogs and cats but not salmonidae — is set for 10 years, for antimicrobials and International Animal Health Journal Corporate Profile We have a full-time archivist, and in-house information technology support.

Our staff are active in many professional organisations and we actively encourage and support the pursuit of continuing education opportunities. Kingfisher International Inc. KFI is a Canadian veterinary contract research organisation CRO whose sole purpose is to improve the lives of companion animals. Maintaining the highest standards of animal welfare is critical to what we do. We have two facilities, totalling 15, sq. In addition to vivarium space we have room for approximately dogs and cats we have a fully-validated clinical pathology laboratory, gross post-mortem suite, surgery suite, and treadmill lab.

We have a solid track record of regulatory acceptance, typically on first pass review. We take pride in ensuring concise, comprehensive, quality submissions that smoothly negotiate the regulatory process. We do, however, routinely conduct non-GLP pilot studies in areas such as pharmacokinetics, bioequivalence, tolerance, and surgical and non-surgical models. At KFI we believe that pilot studies are crucial to establishing appropriate endpoints and determining estimates of statistical variability. Our company was incorporated in and since then, we have conducted both GLP and non-GLP studies on behalf of eight of the top ten companion animal health companies.

Working in this industry allows us to engage with like-minded professionals who see dogs and cats as the target client, and are just as committed as we are to ensuring animal welfare is at the forefront of our research. We are acutely aware that the research we do and our findings have a direct impact on final labelling. Our staff of 25 people include: veterinarians, PhDs, registered veterinary technicians, quality assurance professionals, study coordinators, laboratory technicians, and animal care attendants. Our bioequivalence studies are conducted in compliance with GLP regulations and CVM bioequivalence guidelines to support abbreviated new animal drug applications.

While we do not have in-house bioanalytical capability, we manage all aspects of bioequivalence studies including, but not limited to: in-vivo phase; bioanalytical method development; validation and sample analysis; pharmacokinetics and statistical analysis; final study report; and archiving. At Kingfisher International Inc. We are large enough that we have sufficient resource for complex study designs, yet small enough to ensure that study directors and test facility management are intimately aware of study activities.

We encourage sponsor audits and value the constructive feedback we receive. Since we are located close to Toronto, Canada we are readily accessible to North American and overseas travel. Please contact us to discuss your animal health product development needs! Antimicrobial and other products with special properties such as anabolics, hormones and psychotropics, but also antiinflammatories may only be handled by companies specifically authorised to do so, and additional recordkeeping provisions apply.

Further, protection may be increased by one year for listed species, four years for other species to a maximum of 18 years and in addition five years for clinical trials for MRLs. I have the impression that neither the generic nor the reference companies are too happy with this outcome, so perhaps the Commission has got the balance about right.

Benefit-risk analysis may allow reduced data dossiers for authorisations for minor species and for markets of limited size geographical or for infrequently occurring diseases , but these will be re-assessed after three, then every five, years. Of course, the choice for off-label use in food species is limited to products with MRLs and conservative but practical withdrawal periods based on a multiple of existing withdrawal periods.

However, one area of concern is the strict wording forbidding all food animals in trials involving substances without MRLs from entering the food chain. This seems against 3R principles as well as being a disincentive for innovation. Mitigating the risk of development of antimicrobial resistance is a clear aim of the draft Regulation, which provides the legislative channel for the Commission to tightly control veterinary antimicrobials from authorisation to administration.

Several implementing or delegating acts cover antimicrobials, including lists of antibiotics restricted to human medicine, data gathering on antimicrobial use and off-label restrictions. Antimicrobial resistance is now an integral part of the benefit-risk analysis, with refusal where the perceived risk for public health of development of antimicrobial resistance outweighs the benefits of the product to animal health.

In the separate draft Regulation on Medicated Feeds, preventive use not yet defined of antimicrobials will be banned, animals must be examined by the prescriber, and strict limits on carryover and homogeneity will be enforced. These latter provisions may see many of the feed manufacturers withdraw from handling medicated feeds. Distribution and supply of all veterinary medicines are closely controlled, but authorised distributors and retailers will be able to carry out their business throughout the Union, including retail by internet.

Internet sales will be regulated using the UK model, with authorised retailers displaying a common logo denoting their status, and they will be able to supply in another member state. What exactly are the requirements for generics regarding environmental assessments? Answers may emerge during the co-decision procedure, but so will many more questions and amendments that could significantly change the eventual legal text.

Implementation is not expected before nine years after the process was started. There is a long way to go but in my opinion the proposal provides a good framework for an improved regulatory landscape. The views expressed in this article are my own and not necessarily those of any organisation with which I am associated. Paul Cooper is an independent consultant in Veterinary Regulatory Affairs.

Paul has previously held senior regulatory roles in Merial and was an active member of IFAH Europe regulatory and safety committees. Email: paul. Given the scope and breadth of this subject matter, the discussion here will focus on drug development. Other product types such as devices, diagnostic or otherwise, and foods, are not discussed here and may be revisited in future articles. However, some generalities can be made that cover all product types within the industry.

The FDA, in general, and the CVM have certainly, from my experience in the past several years, emphasised the need for early engagement. If a company, whether new or established, is in the process of developing new products, two major considerations must be taken into account. One, the regulatory environment that could potentially govern the product in question and two, the prevailing intellectual property landscape that could pose a significant barrier to entry if not explored and understood upfront.

Although patenting something is still somewhat of a choice that an entity can exercise some degree of control over, the regulatory requirements governing a particular product are not. They must be complied with and pose more of a risk if the company does not. This information can be based on short-term studies with fairly narrow scientific focus providing justifications, pharmacological and toxicity information, supporting literature and any available pilot studies.

These early communications should also be used to gather information, identify and leverage existing resources, identify issues and gaps of knowledge and perform a risk analysis with the ultimate aim of making a well-informed decision that if left to be made based on the traditional process could end up being extremely costly in time and money. Within the USDA the Center for Veterinary Biologics oversees the development of products that are extracted from biological sources and have medicinal or therapeutic properties biologics.

Approaching the regulatory requirements pragmatically and proactively is not only good for limiting the stress associated with the exercise but also makes perfect economic sense. The principle here is very simple and transcends the type of industry or product involved, if predictability of a process is increased, risk is reduced and the returns become more attractive. This is particularly important given the fact that a blockbuster drug in the animal world only brings in a fraction of the revenue usually associated with a blockbuster drug in the human world.

Having said that, there is plenty of economic value still to be had, and with planning and proactive work the regulatory process may not be as daunting or costly and therefore, adding to the overall economic return of a product. Regulations are unavoidable, and if applied more widely and uniformly, a proactive approach will mitigate the risk and cost of failure and help streamline the approval of new drugs at a faster rate. Similar to the regulatory process, the process for patenting something can be complex, costly and very frustrating, yet for a highly competitive industry with strong growth potential such as the animal health industry, having a robust and successful intellectual property strategy is essential.

Until recently, the United States was the only country in the world with a first-to-invent system versus a first-tofile system. However, in , the United States Congress passed a law that changed the patent system to a first-to-file system, therefore joining the rest of the world. Having said that, the United States still has a special rule that essentially states that if you disclose the invention at a conference or elsewhere, you have a one-year grace period to file a patent for it within the United States. This means that a disclosure will prevent someone else from getting a patent on your invention in the meantime.

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However, that is a double-edged sword because disclosure may hurt the chances of patenting the same invention elsewhere in the world. Given the amount of time and resources to put a single molecule drug, for example, out on the market, the costs of any associated patent or patents may pale into insignificance.

Furthermore, although patents can be challenged and in certain cases circumvented by other clever inventors, having some protection may afford the company that holds the patent some time to recoup some of the costs of bringing the drug to market in the first place. Patent strategies must be crafted to provide operating space in a very crowded industry sector. The engagement of a competent law firm is only one step in the strategy.

Deciding what needs to be protected by a patent and how to design the claims to effectively exclude competitors from the immediate subject matter at the heart of the patent are other aspects that are central to a successful overall strategy. Very few companies approach the issue of patenting in their early stages, mainly because of the costs associated with the patenting process. However, if left until later stages, the patent strategy is more likely to be reactive rather than proactive and may not be as effective in providing exclusivity when the chips fall.

Patents confer exclusivity of use of the subject matter to the patentee, however, there are other instruments that could be employed and that provide exclusivity, albeit for a shorter period of time compared to the protection time covered by an issued patent. Patents are granted by the patent and trademark office and can encompass a wide range of claims.

However, the FDA can grant exclusive marketing rights upon approval of a drug. Exclusivity here is a statutory provision and is granted if certain statutory requirements are met. Exclusivity was designed to promote a balance between new drug innovation and generic drug competition. If evidence is provided that a generic animal drug product has the same active ingredients, in the same concentration, as the approved animal drug product, and that it is bioequivalent to the approved animal drug product, the generic drug may be approved under the GADPTRA.

The law allows a period of three years of marketing exclusivity for a new use of an animal drug and five years of marketing exclusivity for an animal drug that has not been previously approved in any new animal drug application. During those two periods, respectively, no abbreviated applications for a generic copy may be approved for the new use and no abbreviated applications may be submitted. This provision extends the period of protection by US patent for an animal drug, or its method of use, that was approved after November 16, , to compensate for the time that was required for investigation and regulatory review of the animal drug prior to its approval.

Patent term restoration is not related to the exclusivity periods described above and may overlap those exclusivity periods. An outside observer can look at the combined economic impact of the regulations and patent protection mechanisms from two very different points of view. On one hand the regulations and patents can be viewed as counterproductive and a burden on the economy, providing only a net negative in the long run.

Under those circumstances, and if applied across a whole industry sector, an overall positive economic impact cannot be ignored or underestimated. The multiple regulatory hoops to jump through and the seemingly unending costs associated with patenting a new product may appear to be a dark cloud at first; however, upon a more thorough and deliberate second look the same dark cloud may end up with a very prominent silver lining.

References: 1 www. He is also Managing Director for Bimini LLC, a privately owned pet health company manufacturing pet dose-form health supplements and a newly introduced line of pet health treats Email: murrani babylonbioconsulting. Corporate Profile Catching up with Zoetis Canada What does it mean to be an independent global animal health company? It means that Zoetis works hard on the real-world challenges facing those who raise and care for animals, helping to improve outcomes and productivity while bringing new medicines and vaccines to veterinarians.

The Zoetis vision: That our products, services, and people will be the most valued by animal health customers around the world. The Zoetis mission: We build on a six-decade history and singular focus on animal health to bring customers quality products, services, and a commitment to their businesses. Zoetis provides vaccines, parasiticides, anti-infectives, medicated feed additives, and other pharmaceuticals. Our complementary businesses include diagnostics and genetics, as well as services such as dairy data management, hatchery in ovo injection equipment, e-learning, and professional consulting.

Zoetis experts also provide extensive customer service, technical education, and business support across seven core species cattle, horses, poultry, sheep, pigs, cats, and dogs. We aim to help our clients manage their businesses more effectively. Putting our customers first: We strive every day to put our customers first. Zoetis field representatives lead the way by developing beneficial business relationships with customers that endure for years.

Technical and veterinary specialists, who provide in-depth technical expertise and disease education, support these relationships. With extensive on-the-ground presence, Zoetis can react quickly to local-market needs and be well positioned to help our customers continually increase their business productivity and sustain longterm success. When our customers thrive, we thrive. And with this singular focus, Zoetis puts customers first and assists them in making a real difference in the world.

We know how deeply the 30 International Animal Health Journal. Research and Development Zoetis is focused on continuous innovation to develop animal health. We apply our research to a broad and diverse range of species, therapeutic areas, and geographic regions, with research that encompasses vaccines and medicines. Vaccines: Zoetis is a global leader in the research and development of products that help prevent infectious diseases in companion animals and livestock, including poultry and aquaculture. Our research includes modified-live, inactivated and gene-modified approaches to disease prevention.

Medicines: Zoetis is the leader in the identification, research, and development of small and large molecules for therapeutic use in companion animals, and for therapy and improvement of production efficiencies in livestock, poultry, and aquaculture. We seek approaches that improve animal health with a keen eye to environmental sustainability, safety, and food security. Our regional footprint, supported by our in-country and global market research, is at the core of our ability to respond rapidly and accurately when emerging infectious diseases spread and threaten the lives of people, animals, and livelihoods.

Zoetis Canada oversees the care of Looking after 1. Zoetis Canada markets products in Canada; the top sellers in this portfolio are:. Our Diagnostics portfolio consists of more than 90 diagnostic tests, including those that veterinarians can use at point-ofcare and for use in diagnostics-reference laboratories.

Revolution — a topical solution for the treatment and control of fleas, ear mites, sarcoptic mange mites, ticks, and heartworm. Our Poultry Biodevice portfolio consists of devices for both the large and small poultry producer and the manufacturer of egg-based vaccines for either human or veterinary use. Excenel — for the treatment and control of respiratory disease in cattle and swine and foot rot in dairy cattle. These experts leverage stateof-the-art research facilities, and the latest technologies and innovative approaches to deliver complete health solutions to veterinarians and livestock producers.

This worldwide network allows us to listen to livestock producers and veterinarians, region by region, and translate their challenges into practical and costeffective innovations tailored to meet their needs. Draxxin — a single-dose low-volume antibiotic for the treatment of bovine and swine respiratory disease, infectious bovine kerato conjunctivitis and bovine foot rot. Bovishield — a range of viral respiratory and reproductive cattle vaccines. Vanguard — a vaccine that aids in preventing canine distemper caused by canine distemper virus. Working Closely with Each Customer We have the local presence and knowledge to serve the needs of each individual customer, as well as the global reach and resources to help advance animal health around the world.

First and foremost, we strive to form deep, enduring relationships with our customers through the largest direct sales force in the industry. Our sales teams and veterinarians provide expertise and disease education on the ground in more than 70 countries. For health. For you. Introduction Domestic livestock are primary drivers for the livelihood of million farmers in developing countries and contribute to about per cent of agricultural gross domestic product 1.

Delayed detection is often associated with spread of the infection to entire herds and humans. Some zoonoses have spread beyond geographical boundaries and are globalised, e. H1N1, swine flu, Ebola, etc. In countries where such strategies are not legally permitted, livestock keepers are constrained to remain in close contact with the infectious animal, thereby endangering themselves.

Drug resistance to existing therapies, insufficient drug potency, side-effects and drug residues in animal products compound the woes7,8,9. The problems escalate further, when the infections are intracellular. Intracellular Infectious Diseases Intracellular infectious diseases are caused by pathogens that reside within the primary immune defence mechanism of the host, generally comprising macrophages from different reticuloendothelial organs liver, spleen, lymphoid tissues, etc. They are more difficult to eradicate. Extracellular pathogens in contrast survive on epithelial surfaces and extracellular spaces of the body that release specific proteins or toxins triggering body immune mechanism, and are generally more accessible to treatment.

Phagocytosis of organisms following recognition is a natural defence strategy to kill the pathogen. Nevertheless, smart pathogens develop various adaptive mechanisms, survive destruction, and harbour safely within the reticuloendothelial system RES. Common zoonotic infections and their major locations in the RES are listed in Table 1.

Adaptive Mechanism A number of strategies are adopted by smart pathogens to evade death. Bypassing of normal phagocytosis and internalisation into macrophages by alternative pathways, parasitophorous vacuole or receptor-mediated pathways such as clathrin is an important approach Secretion of endolysosomolytic enzymes or endotoxins that break down endosome membrane favour direct entry into the nutrientrich cytosol38, 39 by passing phagolysosomal destruction40, Interference with the phagolysosome formation by either preventing acidification of phagosome, delayed fusion with lysosome, enzymatic breakdown, reduced levels of proton ATPase, disturbances in forming lipid rafts or altering host signal is yet another possibility42, Virulent pathogens also 32 International Animal Health Journal.

These mechanisms are depicted in Figure 1. Figure 1: Uptake and adaptive mechanisms of intracellular pathogens by macrophages 4. Nanotechnology — A Solution Conventional drug delivery strategies rely on diffusion of drug across cell membranes to build up intracellular concentrations. On the other hand, nanocarriers can be designed to follow the same pathway as the virulent organism to enable high drug payloads within the cell. More importantly, nanocarriers also overcome other confronting challenges, namely drug efflux through efflux pumps and Cyp-mediated metabolism.

Targeted delivery of nanocarriers thus presents a promising therapeutic strategy in infectious diseases more specifically. Targeted Drug Delivery The challenges posed for the successful therapy of veterinary infections differ significantly from human infections, not so much in the eradication of the infections, but more so with drug concentration in non-target locations.

Indeed, secretion of drug in milk of lactating animals and residual drug concentrations in meat pose significant hurdles in veterinary therapy. The concept of targeting goes back to the early twentieth century when the Nobel Laureate Paul Ehrlich proposed the magic bullet. The concept, however, has been exploited, although to a limited extent for human therapy, primarily for cancer treatment e. Targeting to the RES can provide a key solution for most livestock intracellular infections.

Passive and active targeting strategies can be exploited to target macrophages. Active targeting using appropriate ligands to facilitate endocytic uptake can further enhance intracellular drug levels. Targeting Volume 1 Issue 2. Spleen, liver, lung, kidney, lymphatic system, bone marrow, intestine, CSF, seminal vesicles, testicles and epididymis. Develops spores preventing breakdown Forms beta- 1,2 glucans and disturbs normal formation of lipid rafts.

Virulence inhibits phagocytosis Survives in phagolysosomes, uptake by non-phagocytic pathway Disrupts phagolysosome and breakdown by enzymes Disrupts phagolysosome. Liver, spleen, adrenal glands, lymph nodes, brain Peripheral blood leukocytes, liver, kidney, lymph node, liver and brain Lymphatic system, lungs, neurons.

Resistant to pH changes Phagosome-lysosome fusion failure Virulence factors increases cytokine production. Box 8 No author can be found. Box 9 Options for author names. Examples for Author 1. Standard journal article on the Internet. Journal article on the Internet with optional limit to the number of authors. Journal article on the Internet with author surnames showing designations of family rank. Journal article on the Internet with author surnames having a prefix, particle, or preposition give as found in the article. Follow the affiliation with a comma placed outside the closing parenthesis, unless it is the affiliation of the last author, then use a period.

Specific Rules for Author Affiliation Abbreviations in affiliations. E-mail address included. Organizational names not in English. Names for cities and countries not in English. Box 10 Abbreviations in affiliations. Box 11 E-mail address included. Box 12 Organizational names not in English. Box 13 Names for cities and countries not in English. Examples for Author Affiliation Journal article on the Internet with author affiliation.

Article Title for Journal Articles on the Internet required General Rules for Article Title Enter the title of an article as it appears on the title page or opening screens. Capitalize only the first word of a title, proper nouns, proper adjectives, acronyms, and initialisms. Use a colon followed by a space to separate a title from a subtitle, unless another form of punctuation such as a question mark, period, or an exclamation point is already present.

End a title with a period unless a question mark or exclamation point already ends it or an Article Type follows it. Article titles in more than one language. Article titles with headers. No article title can be found. Box 14 Article titles not in English. Box 15 Translated article titles ending in punctuation other than a period. Box 16 Article titles in more than one language. Box 17 Article titles containing a Greek letter, chemical formula, or another special character.

Box 18 Article titles with headers. Box 19 No article title can be found. Examples for Article Title Journal article on the Internet not in English. Journal article on the Internet with equal text in two or more languages. Journal article on the Internet with Greek letters or other special characters in the title. Article Type for Journal Articles on the Internet optional General Rules for Article Type An article type alerts the user that the reference is to an abstract of an article or a letter to the editor, not a full article.

Content designator is another phrase for this. Other article types are also available though used less often, such as book review, editorial, or interview. Specific Rules for Article Type Article titles ending in punctuation other than a period. Article titles not in English. Box 20 Articles titles ending in punctuation other than a period. Box 21 Article titles not in English. Examples for Article Type Journal article on the Internet with optional article type. Abbreviate significant words in a journal title see Abbreviation rules for journal titles below and omit other words, such as articles, conjunctions, and prepositions.

Box 22 Abbreviation rules for journal titles. Specific Rules for Journal Title Abbreviation rules for journal titles. Single word journal titles. Non-English journal titles. Journal titles appearing in more than one language. Journals appearing in different editions.

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Options for journal titles. Box 23 Single word journal titles. Box 24 Non-English journal titles. Box 25 Journal titles appearing in more than one language. Box 26 Journals appearing in different editions. Box 27 Options for journal titles. Examples for Journal Title Journal article on the Internet with optional full journal title. Abbreviate each significant word see Abbreviation rules for editions below and omit other words, such as articles, conjunctions, and prepositions.

Specific Rules for Edition Abbreviation rules for editions. Non-English words for editions. Box 29 Non-English words for editions. Examples for Edition Journal article on the Internet with journal title having an edition. Examples for Content Type Journal article on the Internet with optional content type. Specific Rules for Type of Medium Both an edition and a type of medium. Both a content type and a type of medium. Box 30 Both an edition and a type of medium. Box 31 Both a content type and a type of medium. Examples for Type of Medium 1. Date of Publication for Journal Articles on the Internet required General Rules for Date of Publication Include the year, month, and day of publication in that order, such as May 5.

End date information with a semicolon unless there is no volume or issue see No volume or issue follows the date below , then use a colon. Box 36 No volume or issue follows the date. Specific Rules for Date of Publication Further divisions to a date other than volume or issue. Multiple years, months, or days of publication. Non-English names for months.

Seasons instead of months. No volume or issue follows the date. Options for dates. Box 32 Further divisions to a date other than volume or issue. Box 33 Multiple years, months, or days of publication. Box 34 Non-English names for months. Box 35 Seasons instead of months. Box 37 Options for dates. Examples for Date of Publication Journal article on the Internet with season s included in date of publication. Both a date of update and a date of revision. Box 39 Non-English names for months.

Box 40 Seasons instead of months. Box 41 Both a date of update and a date of revision. Examples for Date of Citation 1. Do not follow a volume number with any punctuation unless there is no issue number or other subdivision to the volume, then follow with a colon. Specific Rules for Volume Number Further divisions to volume other than issue. Non-English names for volume. No volume number present. Box 43 Further divisions to a volume other than issue.

Box 44 Non-English names for volume. Box 45 No volume number present. Examples for Volume Number Journal article on the Internet with standard volume and issue. Journal article on the Internet with volume having a subdivision other than an issue. Journal article on the Internet with volume but no issue or other subdivision. Journal article on the Internet without standard volume or issue, but with article number. Journal article on the Internet without standard volume, issue, or article number.

End issue information with a colon unless further divisions, such as a supplement or part, exist see Further divisions to an issue below. Box 46 Further divisions to an issue. Specific Rules for Issue Number Further divisions to an issue. Non-English names for issue. No issue number present.

Options for issues. Box 47 Non-English names for issue. Box 48 No volume number present. Box 49 No issue number present. Box 50 Options for issues. Examples for Issue Number Do not repeat page numbers unless they are followed by a letter. For example: becomes , but AA is correct. Include a letter often S for Supplement or A for Appendix when it precedes the page number, such as S Calculate the extent of the article by the best means possible, i.

Precede the total with the word about and place it in square brackets, such as [about 15 screens]. If the article is printed out, precede the page total with the word about and place it in square brackets, as [about 10 p. Box 54 No numbers appear on the pages of the article. Specific Rules for Location Pagination Roman numerals used as page numbers. Discontinuous page numbers. No numbers appear on the pages of the article. Article numbers used for location. Articles that are videocasts or podcasts.

Box 51 Roman numerals used as page numbers. Box 52 Discontinuous page numbers. Box 53 Text such as a discussion, quiz, or author reply to a letter follows the article. Box 56 Articles that are videocasts or podcasts. Examples for Location Pagination Journal article on the Internet with location expressed as standard page numbers. Journal article on the Internet with a letter included in the page numbers. Journal article on the Internet with indication that a discussion or other text follows it.

Availability for Journal Articles on the Internet required General Rules for Availability Begin with the phrase "Available from" followed by a colon and a space. URLs not directly addressable. Multiple URLs. Box 57 Breaking long URLs. Box 58 URLs not directly addressable. Box 59 Multiple URLs. Examples for Availability 1. Specific Rules for Language Articles appearing in more than one language. Box 60 Articles appearing in more than one language. Examples for Language Notes for Journal Articles on the Internet optional General Rules for Notes Notes is a term for any further information given after the citation.

System requirements. Other types of material to include in notes. Box 61 DOI. Box 62 System requirements. Box 63 Other types of material to include in notes. Examples for Notes Journal article on the Internet with DOI provided. Examples of Citations to Journal Articles on the Internet 1. Journal article on the Internet with optional limit to the number of authors to the first three Terauchi Y, Takamoto I, Kubota N, et al. Journal article on the Internet with compound author surnames Boutin-Foster C. Journal article on the Internet with no author Prevention strategies for asthma--secondary prevention.

Journal article on the Internet with optional article type Davidson A. Journal article on the Internet with date having a supplement Gaal P. Journal article on the Internet with volume but no issue or other subdivision Wolfe L. Journal article on the Internet with issue but no volume Suber P. Journal article on the Internet with a letter included in the page numbers with letter before the numbers Prevention strategies for asthma--secondary prevention.

Journal article on the Internet that is a podcast Tilson J. Journal article on the Internet accompanied by other material Wolfe L. Journal article on the Internet with note Shope JT. Sample Citation and Introduction to Citing Entire Journal Titles on the Internet The general format for a reference to an entire Internet journal title, including punctuation: - for a title continuing to be published:. Include a date of citation in square brackets following the beginning date of publication for a open journal and the ending date of a closed one.

Family Practice [Internet]. Follow a non-English title with a translation when possible; place the translation in square brackets. Specific Rules for Title Journal titles not in English. Journals appearing in more than one language. Box 64 Journal titles not in English. Box 65 Journals appearing in more than one language. Box 66 Journals appearing in different editions. Examples for Title 1. Standard Internet journal title that is still being published.

Specific Rules for Edition Non-English words for editions. Box 67 Non-English words for editions. Examples for Edition 6. Internet journal title with edition. Specific Rules for Editor Names not in English. Box 68 Names not in English. Examples for Editor Internet journal title with current editor name provided. Follow US and Canadian cities with the two-letter abbreviation for the state or province see Appendix E to avoid confusion when citing lesser known cities or when cities in different locations have same name, such as Palm Springs CA and Palm Springs FL.

Follow cities in other countries with the name of the country, either written out or as the two-letter ISO country code see Appendix D , when citing lesser known cities or when cities in different locations have the same name, such as Cambridge MA and Cambridge England. Specific Rules for Place of Publication Locating the place of publication if there is no standard title page. Non-US cities.

Multiple places of publication. No place of publication can be found. Box 69 Locating the place of publication if there is no standard title page. Box 70 Non-US cities. Box 71 Multiple places of publication. Box 72 No place of publication can be found. Examples for Place of Publication Internet journal title with well-known place of publication. Internet journal title with geographic qualifier added to place of publication for clarity.

Internet journal title with unknown place of publication and publisher. Publisher for Journal Titles on the Internet required General Rules for Publisher Record the name of the publisher as it appears in the journal, using whatever capitalization and punctuation are found there. Abbreviate well-known publisher names if desired but with caution to avoid confusion. When a division or other subsidiary part of a publisher is given, enter the publisher name first.

Specific Rules for Publisher Determining the publisher if there is no standard title page. Abbreviated words in publisher names. Non-English publishers. Multiple publishers. Joint publication. No publisher can be found. Using connected vehicle technology to improve the efficiency of intersections. Anderson, M. Subways, strikes, and slowdowns: The impacts of public transit on traffic congestion. Litman, T. Smart congestion relief: Comprehensive analysis of traffic congestion costs and congestion reduction benefits. Wang, S.

Next road rerouting: A multiagent system for mitigating unexpected urban traffic congestion. Mahmassani, H. Urban network gridlock: Theory, characteristics, and dynamics. Surya, B. The processes analysis of urbanization, spatial articulation, social change and social capital difference in the dynamics of new town development in the fringe area of Makassar City case study: In Metro TanjungBunga Area, Makassar City. Daraba, D. Academy of Strategic Management Journal. References : SanaeiNejad, S. In Map Middle East Student, D. Measuring transportation: traffic, mobility and accessibility.

Suryadinata, L. Indonesia's population: Ethnicity and religion in a changing political landscape No. Institute of Southeast Asian Studies. Hill, H. Indonesia's changing economic geography. Giap, T. World Scientific. Firman, T. Springer, Cham. Salusu, J. Ibrahim, M. Pratiwi, F. References : Grimsey, D. Public private partnerships: The worldwide revolution in infrastructure provision and project finance. Edward Elgar Publishing. Brunner, P. Handbook of material flow analysis: For environmental, resource, and waste engineers.

CRC press. Ervianto, W.

PDF CODE Focus Magazine - - Vol. 1 - Issue 2 - Microsoft Office System (Ad-Free!)

Andi Yogyakarta. Oko John, A. Intan, S. Nagapan, S. Yeheyis, M. An overview of construction and demolition waste management in Canada: a lifecycle analysis approach to sustainability. Hoornweg, D. What a waste: a global review of solid waste management. Shen, L. Material wastage in construction activities—a Hong Kong survey.

Hanafi, J. Springer, Berlin, Heidelberg. Willar, D. Improving quality management system implementation in Indonesian construction companies Doctoral dissertation, Queensland University of Technology. Swasto, D. Authors: Aria Syamsu Rizal, M. References : Rushton, A. The handbook of logistics and distribution management: Understanding the supply chain. Kogan Page Publishers. Carmona, M. Public places-Urban spaces. Phillips, D. Looking backward: A critical appraisal of communitarian thought Vol.

Princeton University Press. St-Louis, E. The happy commuter: a comparison of commuter satisfaction across modes. Understanding attitudes towards public transport and private car: A qualitative study. Redman, L. Quality attributes of public transport that attract car users: A research review. Button, K. Transport economics. Travisi, C. Impacts of urban sprawl and commuting: a modelling study for Italy. Aragon, L. Development strategies, religious relations, and communal violence in Central Sulawesi, Indonesia: A cautionary tale.

Palgrave Macmillan, New York. Vickers, A. A history of modern Indonesia. Cambridge University Press. Razdan, R. The evolving Indonesian consumer. References : Cohen, B. Urbanization in developing countries: Current trends, future projections, and key challenges for sustainability. Rodrigue, J. The geography of transport systems. Watson, V. Falk, N. Masterplanning and infrastructure in new communities in Europe. Balsas, C. Sustainable transportation planning on college campuses. Turner, S. Indonesia's small entrepreneurs: Trading on the margins. Jensen, O. Flows of meaning, cultures of movements—urban mobility as meaningful everyday life practice.

Amekudzi, A. Megaregions: Planning for global competitiveness.


  • Table of contents;
  • Season of Singleness.
  • Speech in Action: Interactive Activities Combining Speech Language Pathology and Adaptive Physical Education.
  • The Reluctant Spiritualist: The Life of Maggie Fox;
  • Microsoft Company 15 September 1975;

Island Press. Washington, S. Statistical and econometric methods for transportation data analysis. Urry, J. Mobilities: new perspectives on transport and society. Abdullah, S. Sugiyono, W. Statistikapenelitiandanaplikasinyadengan SPSS Bandung: Alfabeta. Bartholomew, D. Analysis of multivariate social science data. Authors: Rahmadi, Mary Selintung, M. References : Brunekreef, B. Air pollution and health. Promoting ecosystem and human health in urban areas using Green Infrastructure: A literature review.

Colvile, R. The transport sector as a source of air pollution. Air quality guidelines: global update World Health Organization. Hasan, M. A review on the pattern of electricity generation and emission in Indonesia from to Carlson, K. Committed carbon emissions, deforestation, and community land conversion from oil palm plantation expansion in West Kalimantan, Indonesia.

Busch, J. Structuring economic incentives to reduce emissions from deforestation within Indonesia. Van Noordwijk, M. Reducing emissions from land use in Indonesia: motivation, policy instruments and expected funding streams. Ginoga, K. Brauer, M. Ambient air pollution exposure estimation for the global burden of disease Santosa, S. Air pollution and urban air quality management in Indonesia.

Tambunan, T. SME development, economic growth, and government intervention in a developing country: The Indonesian story. Hustim, M. The vehicle speed distribution on heterogeneous traffic: Space mean speed analysis of light vehicles and motorcycles in makassar-indonesia. Aly, S. Authors: Megawati, Rosmariani Arifuddin, M.

References : Jafari, Y. Energy consumption, economic growth and environmental pollutants in Indonesia. Pinto, A. Occupational risk assessment in construction industry—Overview and reflection. Hughes, P. Manning, C. The Manpower Law of and its implementing regulations: Genesis, key articles and potential impact. Fung, I. Developing a risk assessment model for construction safety. Sears, S. Construction project management. Takala, J. Global estimates of the burden of injury and illness at work in Latief, Y.

The nature of fall accidents in construction projects: a case of Indonesia. Reason, J. Managing the risks of organizational accidents. Christina, W. References : Lee, S. Pucher, J. Urban transport trends and policies in China and India: impacts of rapid economic growth. Susilo, Y. A reflection of motorization and public transport in Jakarta metropolitan area.

Winaryo, D. Lyons, G. Travel time use in the information age. Vuchic, V. Urban transit: operations, planning, and economics. Aulia, D. Residential satisfaction of middle income population: Medan city. Maulana, H. Rahman, Z. Analysis of the effect of economic growth toward the center of the overflow area and hinterlend in determining nodal centre of new growth on the area of Mamminasata in South Sulawesi. References : M.

Rahman, L. Bobadilla, A. Mostafavi, T. Carmenate and S. Amicucci and M. King, R. Burdge and H. Suardi R. Sistem Manajemen Keselamatan dan Kesehatan Kerja. Jamil, H. Landis Floyd and D. Asiyanto, Jakarta Misnan, S. Safety Cost in Construction Project. Tao, Q. Shuwen and F. Pindarwati and A. Juniardi, Yulipriyono, E.

Gao and S. Sun, "Multi-link traffic flow forecasting using neural networks," Sixth International Conference on Natural Computation , Yantai, , pp. KebijakanPenanggulanganBanjir di Indonesia. Kodoatie, Robert J. PustakaPelajar : Yogyakarta. Yingchun, "Quantitative research of urban flood-protection project to the added value of real estate: Based on Intervel-valued instuitionistic fuzzy sets theory," International Conference on Consumer Electronics, Communications and Networks CECNet , XianNing, , pp.

Authors: A. Djamaluddin, A. Barakbah, T. Harsono and A. InaTEWS, Veri and T. Sulistiawati, A. Harsono, Y. Yuen A. David, J. Benjamin, F. Evan, W. Dzwinel, A. Zachary, R. Zhang, Z. Jiang and X. Isabella, L. Sampebatu and I. Fariza, N. Abhimata and J. Shodiq, D. Kusuma, M. Rifqi, A. Barakbah and T. Miura, F.

Yamazaki and M. Setyawan, N. Hakim,"Penyusunanpetarisikobencanagempabumiskalamikroberdasarkankerusakanbangunan" , Faculty of Geography Gajah Mada University Yogyakarta Indonesia, Reiter, L. Dong, Z. Shi, H. Su, Y. Liu and W. Luo, Y. Xu and F. Wang, G. Cheng, Y. Gao, A. Long, Z. Xu et al. Wang, H. Chen, Z. Wang, P. Shi, J. Wu, "Decision support system for regional development and water resources coordination", Progress in Geography , vol. Setiawan, EkaWahyu JurnalPenelitian Volume 01 Nomor Wicaksono, Satrio Jakarta Selatan.

Ahsan and S. Morin, B. Marcos, C. Moresoli, C. Laflamme, "Economic and environmental assessment on the energetic valorization of organic material for a municipality in Quebec, Canada", Applied Energy 87 Khelidj, B. Abderezzak and A. Sulistyo, S. Syamsiah, D. Herawati and A. Wahyuni, Sri. PanduanPraktis Biogas. Hanif, Andi. Simeon, TorbiraMtamabari. Department of Mechanical Engineering University of Nigeria. Herawati, Tati. Volume 22, No. Sudarno, Fadelan. Volume 18, No.

Guangdong GongLu Jiao Tong, , 3 Nicholas E. Lownes, Randy B. Ejercito, K. Nebrija, R. Feria and L. Chen, X. Zhang and G. Du and D. Bede, B. Yulianto, Budi danSetiono. Surakarta :UniversitasSebelasMaret. Putri, NurjannahHaryanti. Yogyakarta: UniversitasGadjahMada. Horonjeff, Y. Kimural, N. Rossano, Aircraft Management Studies. Kazda and B. Caves, Airport Design and Operation Bethary, Pradana and Basidik43, Authors: Wulandari Alwinda Puspasari , M. Isran Ramli, S. Indonesia, R. Saffan and M. Dewanti, D. Achmad and P. Siregar, JurnalEkbis 16, 12 DepartemenPerhubungan R.

I DirektoratJenderalPerhubunganDarat. Aviasti, A. Panjaitan, I. Probabilistic structural mechanics handbook: theory and industrial applications. Wu, and S. Zhao, Natural Hazards 77, Noor, L. Sidek, H. Basri, M. Husni, A. Jaafar, M. Mohammad, and S. San and M. Emami, S. Sadigh, and A. Margheritini, D. Vicinanza, and P. Frigaard, Renewable Energy 34, Contestabile, F. Vincenzo, E. Lauro, and D. Vicinanza, Coastal Engineering Proceedings 1, 12 Ahmad, M. Musa, A. Maliki, O. Yaakob, K. Samo, and M. Ibrahim, Journal of Environmental Science and Technology 9, Troch, J. Mollaert, S.

Peelman, L. Victor, J. Meer, D. Kortenhaus, Coastal Engineering Proceedings 1, 2 Liu, Z. Han, H. Shi, and W. References : R. Faizah, W. Hartono and S. Sugiyarto, JurnalManajemen Dan Organisasi 1, 80 Pangkey, G. Al-Anbari, A. Khalina, A. Alnuaimi, A. Normariah, and A. Vasconcelos and B. Wariishi and T. Hughes and E.