NEwPORT INDUSTRY INFORMATION GLOSSARY OF INDUSTRY TERMSAbbreviAted New drug ApplicAtioN (ANdA) ANdeAN commuNity of NAtioNs Newport product offeriNgsAn Abbreviated New Drug Application (ANDA) contains A trade bloc comprising Bolivia, Colombia, Ecuador anddata that, when submitted to FDA’s Center for Drug Peru. Venezuela withdrew membership in 2006. For Generics & API ManufacturersEvaluation and Research, Office of Generic Drugs, Newport for generics —provides for the review and ultimate approval of a premium, global, and sourcing ApprovAl letter packagesgeneric drug product in the US. An official communication from FDA to a new drug For InnovatorsGeneric drug applications are called “abbreviated” application (NDA) sponsor that allows the commercial Newport for innovators —because they are generally not required to include marketing of the product. premium, global, and sourcingpreclinical (animal) and clinical (human) data to packagesestablish safety and effectiveness. Instead, a generic Atc codeapplicant must scientifically demonstrate that its Anatomical Therapeutic Chemical classification system. iNdustry liNksproduct is bioequivalent. governmental / regulatoryOnce approved, an applicant may manufacture and bioAvAilAbility organizationsmarket the generic drug product. The rate and extent at which an active pharmaceutical trade shows & conferences ingredient is absorbed (both speed and amount) by theActive moiety body when introduced in a given dosage form (capsule,In chemistry, a moiety is a group of atoms forming part tablet, injectable, suppository, etc).of a molecule. In the case of a pharmaceutical product,the active moiety is that part of the molecule of an active bioequivAleNcesubstance which gives it its therapeutic effect. Two medicines are bioequivalent when they contain the same amount of an identical active pharmaceuticalActive phArmAceuticAl iNgredieNt ingredient, and when their bioavailability is the sameAn active pharmaceutical ingredient is any component when administered in equal doses under equalthat provides pharmacological activity or other direct conditions. Strict scientific criteria exist for runningeffect in the diagnosis, cure, mitigation, treatment, or bioequivalence studies.prevention of disease, or to affect the structure or anyfunction of the body of man or animals. biogeNeric/biosimilAr product An off-patent biological medicinal product which isMost generic companies depend on independent produced by manufacturers other than the originatorAPI manufacturers for the active ingredients that go and which is similar to the originator product.into their products. APIs are important because their Biogenerics are sometimes called biosimilar or follow-successful development and manufacture is critical to on biologic products because biological productsgeneric development and production. produced by different manufacturers are not strictlyFrom a generic company perspective, knowledge of identical, but similar.API availability and bulk producers’ manufacturing Once approved by the competent authorities,capabilities and regulatory histories facilitates business biosimilar/biogeneric products are not significantlydevelopment and partnering decisions. From a brand different in terms of quality, safety and efficacy from thecompany perspective, knowledge of activity in the API originator product.market can be predictive of generic activity well inadvanced of brand exclusivity expiry.Alternative terms for API include “bulk”, “raw material”,and “pharmaceutical ingredients”.AfricAN regioNAl iNtellectuAl propertyorgANizAtioN (Aripo)A patent resource pooling agreement that coversBotswana, the Gambia, Ghana, Kenya, Lesotho, Malawi,Mozambique, Namibia, Sierra Leone, Somalia, Sudan,Swaziland, Tanzania, Uganda, Zambia and Zimbabwe.
Newport iNdustry iNformAtioNbiologic liceNse ApplicAtioN (blA) ceNtrAlised procedureBiological products are approved for marketing in the The Centralised Procedure is one of two differentUS under the provisions of the Public Health Service routes for authorizing medicinal products for marketing(PHS) Act. The Act requires a firm who manufactures a and use in the European Union. It entails submissionbiologic for sale in interstate commerce to hold a license of an application to the EMEA and is obligatory forfor the product. certain pharmaceuticals, such as those derived from biotechnology, and is optional for others.A biologics license application is a submission thatcontains specific information on the manufacturing The marketing authorization granted is valid in allprocesses, chemistry, pharmacology, clinical countries of the EEA. See: Decentralised Procedure andpharmacology and the medical affects of the biologic Mutual Recognition Procedure.product. If the information provided meets FDArequirements, the application is approved and a license certificAtes of suitAbility (cep)is issued allowing the firm to market the product. From the perspective of the European Pharmacopeia: where the Convention on the Elaboration of a Europeanbiologic product Pharmacopoeia is applied, it is essential to have aA biologic product is any virus, serum, toxin, antitoxin, procedure that allows the manufacturer of a substancevaccine, blood, blood component or derivative, to provide proof that the purity of the substance isallergenic product, or analogous product applicable suitably controlled by the monograph of the Europeanto the prevention, treatment, or cure of diseases or Pharmacopoeia.injuries. Biologic products are a subset of drug products The procedure described in Resolution AP-CSP (99)distinguished by their manufacturing processes 4 of the Council of Europe satisfies this need through(biological process vs. chemical process). In general, the certificate of suitability monographs of the Europeanterm “drugs” includes biologic products. Pharmacopoeia granted by the EDQM.biologicAl mediciNAl product Further support for EU wide certificates is suppliedA medicine where the active substance is a biological by directives 75/318/EEC amended and 81/852/EECsubstance as opposed to a chemical substance. The amended on quality, safety and efficacy criteria forbiological substance is produced by or extracted from a marketed medicinal products. The requirements on thebiological source. quality of active substances are given in the Guideline “Requirements in relation to active substances”bolAr AmeNdmeNt published in Vol III, add No 2, May 1992 (pp 29-34) of the European Community regulations on medicines.Roche Products, Inc. v. Bolar Pharmaceutical Co., 733F.2d 858 (Fed. Cir. 1984), in which the Federal Circuit The European Pharmacopoeia is comprised of 28 parties toheld that the manufacture, use, or sale of a patented the Convention: 26 member states of the Council of Europeinvention during the term of the patent constituted an (including the 15 states of the European Union): Austria,act of infringement, even if it was for the sole purpose of Belgium, Croatia, Cyprus, the Czech Republic, Denmark,conducting tests and developing information necessary Finland, the former Yugoslav Republic of Macedonia,to apply for regulatory approval. France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Luxembourg, the Netherlands, Norway, Portugal, thebrANd NAme drug Slovak Republic, Slovenia, Spain, Sweden, Switzerland,A brand name drug is a drug marketed under a Turkey and the United Kingdom; one state not a memberproprietary, trademark-protected name. of the Council of Europe: Bosnia and Herzegovina; and the Commission of the European Communities.cAs Numbers ctdChemical Abstracts Service Registry numbers. A unique,numerical designation for every chemical, including Common Technical Document.pharmaceuticals. dAtA exclusivityCAS numbers are used primarily by chemists to In the EU, the period of time during which the medicinesidentify different drugs, since the text names of drugs authorities are not allowed to consult the dossier ofcan vary. CAS numbers are assigned by the American an originator pharmaceutical to verify the safety andChemical Society’s Chemical Abstracts Service (CAS), efficacy of the active moiety in the application forgenerally determined with the rules of the International marketing authorization of a generic medicine.Union of Pure and Applied Chemistry (IUPAC) and theInternational Union of Biochemistry (IUB). Registry Data exclusivity periods may extend beyond thenumbers are assigned randomly and do not imply any patent protection period of a pharmaceutical product,compositional or other meaning. thus delaying the availability of lower-priced generic medicines to patients.
Newport iNdustry iNformAtioNdeceNtrAlised procedure in their manufacture must be covered in a DMF orThe Decentralized Procedure represents a new means other FDA document (such as an NDA).of applying for marketing authorizing for a generic • Type IV: Excipient, colorant, flavor, essence ormedicine in the EU. It consists of a single application material DMF. Excipients are chemically inactivesubmitted simultaneously to all Member States, who substances such as starches or cellulose used towill determine the merits of the application collectively. bind drug powder together so that it can be pressed into a tablet. Other examples include flavorings indosAge form children’s drugs, alcohol in liquids, etc.A dosage form is the physical form in which a drug is • Type V: FDA accepted reference information notproduced and dispensed, such as a tablet, a capsule, or included in Types I-IV.an injectable. Starting in September, 1998 the FDA began to declare some DMFs inactive. The criteria for judging a DMF todrug be inactive, as listed on the FDA website, include:A drug is defined as: • The holder requested that the DMF be retired or• A substance recognized by an official inactivated. pharmacopoeia or formulary. • DMFs filed more than 6 years ago which have had• A substance intended for use in the diagnosis, cure, no activity. mitigation, treatment, or prevention of disease. • DMFs filed more than 6 years ago which have had• A substance (other than food) intended to affect the only one or two submissions within the past 6 years. structure or any function of the body. • DMFs which have not had an annual update from• A substance intended for use as a component of a the holder for the past 5 years. medicine but not a device or a component, part or accessory of a device. Historically, filing a DMF was a way for less established firms to claim a degree of credibility when trying to• Biologic products are included within this definition sell into the US market and even in other regulated and are generally covered by the same laws and markets. However, since DMFs are only reviewed when regulations, but differences exist regarding their an ANDA or NDA references them, a DMF that has not manufacturing processes (chemical process vs. been referenced is of questionable value even if the biological process). DMF holder thinks having a DMF makes them look legitimate. Filing DMFs without any customers in the USdrug mAster file ( dmf) has become much less common, so more recent DMFsA confidential document filed by API manufacturers are a better indicator of intent to manufacture thanand referenced in an Abbreviated New Drug Application older DMFs.(ANDA) or New Drug Application (NDA).Since a DMF is required to supply bulk material to the drug productUS market, API manufacturers with a large number The finished dosage form that contains a drugof DMFs tend to be more reliable in terms of quality, substance, generally, but not necessarily in associationregulatory standing, and ability to meet cGMP. It should with other active or inactive ingredients.be noted, however, that DMFs are only reviewed after adose form filing references that DMF. Therefore, not all edqmDMFs are reviewed by the FDA, and the possession of a European Directorate for the Quality of Medicines of theDMF for a product does not ensure that a manufacturer Council of Europe.is producing that product or able to supply it to the US.There are five types: emeA The European Medicines Agency is responsible for• Type I: Facilities DMF. Manufacturing site, facilities, evaluating medicinal products and providing advice on operating procedures and personnel not specific to a research and development programs and maintaining drug substance. Type I DMFs are no longer accepted various databases available to healthcare professionals by the FDA but old ones remain on file. and the public. It is also responsible for granting single• Type II: Drug substance DMF. Drug substances, European marketing authorizations for medicines intermediates and materials used in their through the Centralized Procedure and for arbitrating in preparation. A Type II DMF can also cover dosage case of disputes. form drugs manufactured under contract for another company which would file an ANDA. Type II is the most common form of DMF.• Type III: Packaging material DMF. Packaging materials, from bottles and caps to PVC resin used
Newport iNdustry iNformAtioNeu FDA requires many rigorous tests and procedures toA trade bloc comprising: Austria, Belgium, Bulgaria, assure that the generic drug can be substituted forCyprus, the Czech Republic, Denmark, Estonia, Finland, the brand name drug. The FDA bases evaluations ofFrance, Germany, Greece, Hungary, Ireland, Italy, Latvia, substitutability, or “therapeutic equivalence,” of genericLithuania, Luxembourg, Malta, the Netherlands, Poland, drugs on scientific evaluations.Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, By law, a generic drug product must contain theUnited Kingdom. identical amounts of the same active ingredient(s) as the brand name product. Drug products evaluated aseurAsiAN pAteNt coNveNtioN (eApo) “therapeutically equivalent” can be expected to haveA regional organization to grant Eurasian patents, equal effect and no difference when substituted for thecomprising: the Republic of Armenia, the Azerbaijan brand name product.Republic, the Republic of Belarus, the Republicof Kazakhstan, the Kirghiz Republic, the Republic grANdfAtheriNgof Moldova, Russia, the Republic of Tajikistan, A clause within the implementing language for GATTTurkmenistan. in the US that allows a company that had madeeuropeAN pAteNt orgANisAtioN (epo) “substantial investment” in a generic pharmaceutical prior to the GATT extension of certain patent expiryA patent granting body comprising: Austria, Belgium, dates to market a generic version of the product onBulgaria, Cyprus, Czech Republic, Denmark, Estonia, which the patent has been extended provided that theFinland, France, Germany, Greece, Hungary, Iceland, generic company pay a “reasonable remuneration” toIreland, Italy, Latvia, Liechtenstein, Lithuania, the patentee.Luxembourg, Malta, Monaco, Netherlands, Poland,Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Neither “substantial investment” nor “reasonableSwitzerland, Turkey, United Kingdom. remuneration” were defined in the GATT implementing legislation and the courts are expected to decide how toexpiry dAte define these terms.The end date of the patent term. The duration of a hAtch-wAxmAN Actpatent differs from country to country and the startingpoint of patent life may be the local filing date, See waxman-Hatch Act.publication date, date of grant, etc. As a general rule,the expiry date is usually not later than 21 years from ichpriority (ie 20 years from local filing in most countries). International Conference on Harmonization.when a patent has reached the end of its term, it is said iNNto have expired. Patents may cease before the normalexpiry date for a variety of reasons e.g. for non-working of International Non-proprietary Names. The official,the invention, or through non-payment of renewal fees. international standard for generic pharmaceutical names. Similar to the USAN, but there is some variation betweenfdA the names. NPS uses the INN and provides appropriate synonyms from the USAN as well as brand names.United States Food and Drug Administration. mutuAl recogNitioN procedure (mrp)first mArketiNg AuthorizAtioN Mutual Recognition Procedure is one of two routesThe First Marketing Authorization information is the currently available for authorizing medicinal productsdate and country of the first marketing authorization for marketing in more than one country of thewithin the EU. The date of the first EU marketing European Union.authorization is the reference date for all SPCs grantedin the EU. The MRP is available for most conventional medicines and consists of the marketing authorization grantedgAtt in one EU Member States being recognized as valid inGeneral Agreement on Trade and Tariffs, superseded by other Member States upon request. The EMEA servesthe world Trade Organization (wTO) in January 1995. as arbiter in case of disputes between the concernedThe GATT 1994 Agreement is an integral part of the parties over the application.world Trade Organization Agreement.geNeric drugA generic drug is the same as a brand name drugin dosage, safety, strength, how it is taken, quality,performance, and intended use. In the case of theUS, before approving a generic drug product, the
Newport iNdustry iNformAtioNNew drug ApplicAtioN (NdA) pctwhen the sponsor of a new drug believes that enough Patent Cooperation Treaty.evidence on the drug’s safety and effectiveness has beenobtained to meet the FDA’s requirements for marketing priorityapproval, the sponsor submits to FDA a new drug The initial patent application, usually in the country ofapplication (NDA). The application must contain data the invention, establishes the priority date (the datefrom specific technical viewpoints for review, including from which the invention is taken to be novel) and thechemistry, pharmacology, medical, biopharmaceutics, priority number (the local application number) ofand statistics. the invention.If the NDA is approved, the product may be marketedin the US. For internal tracking purposes, all NDAs are product fAmilyassigned an NDA number. This information is intended to imply that either a trivial chemical processing relationship or a late stageorANge book intermediate/final product relationship exist betweenThe FDA’s list of Approved Drug Products with products within a product family.Therapeutic Equivalences is commonly referred to Different salts of a specific product are considered to beas “The Orange Book.” The FDA’s official publication, within the same product family, ie. erythromycin estolateit covers, among other things, approved generic, is in the same product family as erythromycin palmitatedose form dossiers, non-antibiotic patent expiries since they are both readily produced from erythromycin.and waxman-Hatch extension information forpharmaceuticals in the US. This information serves to identify sources of material that are likely to have the capability of supplying orThe Orange Book is linked to Newport’s proprietary producing products even if they are not currentlyintelligence on API manufacturing worldwide, patent producing the specified product.data and DMF and AADA data from the FDA as part ofNMLAdvanced. summAry of product chArActistics (smpc) The SmPC is a full, official description of aorgANisAtioN AfricAiNe de lA propriete pharmaceutical product, which lists the name of theiNtellectuelle ( oApi) active substance, its composition, uses, dosages,A patent application organization comprising: Benin, pharmaceutical forms, and known adverse reactions,Burkina Faso, Cameroon, Central Africa, Chad, Congo, amongst other information.Cote d’Ivoire, Equatorial Guinea, Gabon, Guinea, GuineaBissau, Mali, Mauritania , Niger, Senegal, Togo. The SmPC is the basis of information for health professionals on how to use the medicinal productpAteNt safely and effectively. The condensed version provided to patients with the medicine in the form of a “patientA patent is a temporary monopoly given by law to an information leaflet” (PIL) must be written in languageinventor which allows the inventor to prevent others that is easily understood by non-professionals.from exploiting the invention. In return, the inventormust make a full disclosure of the invention. The supplemeNtAry protectioN certificAte (spc)disclosure, which is a patent, must be such that a personskilled in the art would be able to work the invention. SPCs were introduced by the EU, and provide up to five years’ protection from the date of patent expiry, upPatent laws were originally created to provide inventors to a maximum of 15 years from the date of marketingwith an incentive to create new inventions by giving authorization, for products, processes and methodsthem temporary protection from competition. Today, the of use.patent protection period gives inventors the opportunityto recoup their R&D investments in new products either Applications for SPCs must be made to the authorityby direct manufacture and sale or by licensing. which granted the patent within six months of marketing authorization being granted (or within sixpAteNt fAmily months of a patent being granted when authorization precedes the grant of a patent).A group of patents claiming, as far as local laws allow,the same invention (same patent) in different countries.pAteNteeThe patent holder. The name of the company, notthe name of the person who filed the patent. Thecorporation is also identified in cases where there is adifferent parent company.
Newport iNdustry iNformAtioNtherApeutic clAss provide product patents by January 1 1995), and theA system for grouping pharmaceuticals based on least developed countries have 11 years.similar therapeutic effect. A large number of distinctclassifications have been compiled. usAN United States Adopted Names. The official standard forTwo classifications are utilized: the Therapeutic generic names in the USA.category assigned by the Merck Index (based on theUSAN assignment) and the Anatomical Therapeutic voided certificAtesclassification based on the European PharmaceuticalMarket Research Association (EPhMRA) Anatomical See Certificates of Suitability (CEP).classification, which organizes therapeutic categories ina hierarchy. wAxmAN-hAtch Act The Patent Term Restoration and Price Competition ActtherApeutic equivAleNcy code passed by the US in 1984. Congressman waxman ofThe coding system developed by Thomson Reuters for California and Senator Hatch of Utah were key architectstherapeutic equivalence, designed to allow users to of this historic piece of compromise legislation betweenquickly determine if the FDA has evaluated a particular the brand name and generic drug industries.product as therapeutically equivalent to an approved The waxman-Hatch Act provided the brand nameproduct and to provide some information on the basis industry with a period of marketing exclusivity of upof this comparison. In the most common example, a to five years to compensate for the extended period ofgeneric drug is evaluated to determine equivalence to FDA review of a New Drug Application (NDA). In return,an approved branded drug. drugs coming off patent were eligible for a simpler,Therapeutic equivalence codes consist of two letters. quicker FDA review process involving submission of anProducts that are considered to be therapeutically Abbreviated New Drug Application (ANDA).equivalent are given the “A” designation as their first waxman-Hatch provided for marketing exclusivityletter, while those considered not therapeutically periods for non-antibiotic and non-biological products.equivalent are given the “B” designation. Codes AA, For patent extensions under the Act, which was enactedAN, AO, AP, and AT indicate no known bioequivalence September 24 1984, the patent-holder can apply toproblems, while the designation AB indicates that actual have the term of a patent extended for up to five years,or potential bioequivalence problems were resolved. up to a maximum of 14 years from NDA approval.Codes BC, BD, BE, etc all indicate non-equivalence. The actual extension period is based on the time takenThe AB rating is common for generic drugs where a by the regulatory review after the grant of the patentparagraph IV filing is used to circumvent a certain (half of the testing period plus the full NDA approvalinnovator patent, and the innovator then challenges this period): the extension period may be reduced if some ofnew formulation on the grounds of non-bioequivalence. the time lost during this period is considered to be dueOnce bioequivalence is demonstrated to the FDA, the to the patent-holder. The patent-holder may choosegeneric would receive an AB rating. which patent (product, process or use) on a product is to be extended, but a patent may be extended only once.tripsTrade Related aspects of Intellectual Property Rights. world iNtellectuAl property orgANizAtioNThe TRIPs agreement sets standards of protection and (wipo)addresses enforcement procedures for intellectual A specialized agency of the United Nations (UN)property (IP) rights of wTO member countries. with responsibility for promoting the protection ofMajor provisions include: patent protection for intellectual property and for administering a number ofpharmaceutical products; pharmaceutical patent international treaties, including the Paris Convention. Itprotection of 20 years from the date of filing; provides services for the international registration andlimitations on compulsory licensing and a ban on filing of patents and trademarks, and facilitates thespecific compulsory licensing requirements for certain settlement of intellectual property disputes.technologies; grant of patents is not dependent on local wIPO is responsible for the revision of the variousmanufacture. treaties which it administers. It also prepares newCountries which did not provide product patent treaties and conducts studies on intellectual propertyprotection at January 1 1995 must provide: a means issues. A substantial training and advisory program isfor filing product patent applications; an exclusive carried out for the benefit of developing countries.marketing right of up to five years.Developed countries have one year to incorporate theagreement into national law, developing countries havefive years (10 years for product patents if they didn’t