What are intellectual property rights?Intellectual property rights are the rights given to persons over the creations of their minds. They usually give the creator an exclusive right over the use of his/her creation for a certain period of time.

Intellectual property rights are customarily divided into two main areas:

(i) Copyright and rights related to copyright. back to top

The rights of authors of literary and artistic works (such as books and other writings, musical compositions, paintings, sculpture, computer programs and films) are protected by copyright, for a minimum period of 50 years after the death of the author.

Also protected through copyright and related (sometimes referred to as “neighbouring”) rights are the rights of performers (e.g. actors, singers and musicians), producers of phonograms (sound recordings) and broadcasting organizations. The main social purpose of protection of copyright and related rights is to encourage and reward creative work.

 (ii) Industrial property. back to top

Industrial property can usefully be divided into two main areas:

One area can be characterized as the protection of distinctive signs, in particular trademarks (which distinguish the goods or services of one undertaking from those of other undertakings) and geographical indications (which identify a good as originating in a place where a given characteristic of the good is essentially attributable to its geographical origin).

The protection of such distinctive signs aims to stimulate and ensure fair competition and to protect consumers, by enabling them to make informed choices between various goods and services. The protection may last indefinitely, provided the sign in question continues to be distinctive.

Other types of industrial property are protected primarily to stimulate innovation, design and the creation of technology. In this category fall inventions (protected by patents), industrial designs and trade secrets.

The social purpose is to provide protection for the results of investment in the development of new technology, thus giving the incentive and means to finance research and development activities.

A functioning intellectual property regime should also facilitate the transfer of technology in the form of foreign direct investment, joint ventures and licensing.

The protection is usually given for a finite term (typically 20 years in the case of patents).

While the basic social objectives of intellectual property protection are as outlined above, it should also be noted that the exclusive rights given are generally subject to a number of limitations and exceptions, aimed at fine-tuning the balance that has to be found between the legitimate interests of right holders and of users.

rigins: into the rule-based trade system.... back   to   top

Ideas and knowledge are an increasingly important part of trade. Most of the value of new medicines and other high technology products lies in the amount of invention, innovation, research, design and testing involved. Films, music recordings, books, computer software and on-line services are bought and sold because of the information and creativity they contain, not usually because of the plastic, metal or paper used to make them. Many products that used to be traded as low-technology goods or commodities now contain a higher proportion of invention and design in their value — for example brandnamed clothing or new varieties of plants.

Creators can be given the right to prevent others from using their inventions, designs or other creations — and to use that right to negotiate payment in return for others using them. These are “intellectual property rights”. They take a number of forms. For example books, paintings and films come under copyright; inventions can be patented; brandnames and product logos can be registered as trademarks; and so on. Governments and parliaments have given creators these rights as an incentive to produce ideas that will benefit society as a whole.

The extent of protection and enforcement of these rights varied widely around the world; and as intellectual property became more important in trade, these differences became a source of tension in international economic relations. New internationally-agreed trade rules for intellectual property rights were seen as a way to introduce more order and predictability, and for disputes to be settled more

  

Types of intellectual property

The areas covered by the TRIPS Agreement

Copyright and related rightsTrademarks, including

service marksGeographical indicationsIndustrial designsPatentsLayout-designs

(topographies) of integrated circuits

Undisclosed information, including trade secrets

systematically.

The Uruguay Round achieved that. The WTO’s TRIPS Agreement is an attempt to narrow the gaps in the way these rights are protected around the world, and to bring them under common international rules. It establishes minimum levels of protection that each government has to give to the intellectual property of fellow WTO members. In doing so, it strikes a balance between the long term benefits and possible short term costs to society. Society benefits in the long term when intellectual property protection encourages creation and invention, especially when the period of protection expires and the creations and inventions enter the public domain. Governments are allowed to reduce any short term costs through various exceptions, for example to tackle public health problems. And, when there are trade disputes over intellectual property rights, the WTO’s dispute settlement system is now available.

The agreement covers five broad issues:

  how basic principles of the trading system and other international intellectual property agreements should be applied

  how to give adequate protection to intellectual property rights

  how countries should enforce those rights adequately in their own territories

  how to settle disputes on intellectual property between members of the WTO

  special transitional arrangements during the period when the new system is being introduced.

Basic principles: national treatment, MFN, and balanced protection back   to   top

As in GATT and GATS, the starting point of the intellectual property agreement is basic principles. And as in the two other agreements, non-discrimination features prominently: national treatment (treating one’s own nationals and foreigners equally), and most-favoured-nation treatment (equal treatment for nationals of all trading partners in the WTO). National treatment is also a key principle in other intellectual property agreements outside the WTO.

The TRIPS Agreement has an additional important principle:

intellectual property protection should contribute to technical innovation and the transfer of technology. Both producers and users should benefit, and economic and social welfare should be enhanced, the agreement says.

How to protect intellectual property: common ground-rules back   to   top

The second part of the TRIPS agreement looks at different kinds of intellectual property rights and how to protect them. The purpose is to ensure that adequate standards of protection exist in all member countries. Here the starting point is the obligations of the main international agreements of the World Intellectual Property Organization (WIPO) that already existed before the WTO was created:

  the Paris Convention for the Protection of Industrial Property (patents, industrial designs, etc)

  the Berne Convention for the Protection of Literary and Artistic Works (copyright).

Some areas are not covered by these conventions. In some cases, the standards of protection prescribed were thought inadequate. So the TRIPS agreement adds a significant number of new or higher standards.

Copyright back   to   top

The TRIPS agreement ensures that computer programs will be protected as literary works under the Berne Convention and outlines how databases should be protected.

It also expands international copyright rules to cover rental rights. Authors of computer programs and producers of sound recordings must have the right to prohibit the commercial rental of their works to the public. A similar exclusive right applies to films where commercial rental has led to widespread copying, affecting copyright-owners’ potential earnings from their films.

The agreement says performers must also have the right to prevent unauthorized recording, reproduction and broadcast of live performances (bootlegging) for no less than 50 years. Producers of sound recordings must have the right to prevent the unauthorized reproduction of recordings for a period of

50 years.

Trademarks back   to   top

The agreement defines what types of signs must be eligible for protection as trademarks, and what the minimum rights conferred on their owners must be. It says that service marks must be protected in the same way as trademarks used for goods. Marks that have become well-known in a particular country enjoy additional protection.

Geographical indications back   to   top

A place name is sometimes used to identify a product. This “geographical indication” does not only say where the product was made. More importantly, it identifies the product’s special characteristics, which are the result of the product’s origins.

Well-known examples include “Champagne”, “Scotch”, “Tequila”, and “Roquefort” cheese. Wine and spirits makers are particularly concerned about the use of place-names to identify products, and the TRIPS Agreement contains special provisions for these products. But the issue is also important for other types of goods.

Using the place name when the product was made elsewhere or when it does not have the usual characteristics can mislead consumers, and it can lead to unfair competition. The TRIPS Agreement says countries have to prevent this misuse of place names.

For wines and spirits, the agreement provides higher levels of protection, i.e. even where there is no danger of the public being misled.

Some exceptions are allowed, for example if the name is already protected as a trademark or if it has become a generic term. For example, “cheddar” now refers to a particular type of cheese not necessarily made in Cheddar, in the UK. But any country wanting to make an exception for these reasons must be willing to negotiate with the country which wants to protect the geographical indication in question.

The agreement provides for further negotiations in the WTO to establish a multilateral system of notification and registration of geographical indications for wines. These are now part of the Doha Development Agenda and they include spirits. Also debated in the WTO is whether to negotiate extending this higher level of protection beyond wines and spirits.

Industrial designs back   to   top

Under the TRIPS Agreement, industrial designs must be protected for at least 10 years. Owners of protected designs must be able to prevent the manufacture, sale or importation of articles bearing or embodying a design which is a copy of the protected design.

Patents back   to   top

The agreement says patent protection must be available for inventions for at least 20 years. Patent protection must be available for both products and processes, in almost all fields of technology. Governments can refuse to issue a patent for an invention if its commercial exploitation is prohibited for reasons of public order or morality. They can also exclude diagnostic, therapeutic and surgical methods, plants and animals (other than microorganisms), and biological processes for the production of plants or animals (other than microbiological processes).

Plant varieties, however, must be protectable by patents or by a special system (such as the breeder’s rights provided in the conventions of UPOV — the International Union for the Protection of New Varieties of Plants).

The agreement describes the minimum rights that a patent owner must enjoy. But it also allows certain exceptions. A patent owner could abuse his rights, for example by failing to supply the product on the market. To deal with that possibility, the agreement says governments can issue “compulsory licences”, allowing a competitor to produce the product or use the process under licence. But this can only be done under certain conditions aimed at safeguarding the legitimate interests of the patent-holder.

If a patent is issued for a production process, then the rights

must extend to the product directly obtained from the process. Under certain conditions alleged infringers may be ordered by a court to prove that they have not used the patented process.

An issue that has arisen recently is how to ensure patent protection for pharmaceutical products does not prevent people in poor countries from having access to medicines — while at the same time maintaining the patent system’s role in providing incentives for research and development into new medicines. Flexibilities such as compulsory licensing are written into the TRIPS Agreement, but some governments were unsure of how these would be interpreted, and how far their right to use them would be respected.

A large part of this was settled when WTO ministers issued a special declaration at the Doha Ministerial Conference in November 2001. They agreed that the TRIPS Agreement does not and should not prevent members from taking measures to protect public health. They underscored countries’ ability to use the flexibilities that are built into the TRIPS Agreement. And they agreed to extend exemptions on pharmaceutical patent protection for least-developed countries until 2016. On one remaining question, they assigned further work to the TRIPS Council — to sort out how to provide extra flexibility, so that countries unable to produce pharmaceuticals domestically can import patented drugs made under compulsory licensing. A waiver providing this flexibility was agreed on 30 August 2003.

Integrated circuits layout designs back   to   top

The basis for protecting integrated circuit designs (“topographies”) in the TRIPS agreement is the Washington Treaty on Intellectual Property in Respect of Integrated Circuits, which comes under the World Intellectual Property Organization. This was adopted in 1989 but has not yet entered into force. The TRIPS agreement adds a number of provisions: for example, protection must be available for at least 10 years.

Undisclosed information and trade secrets back   to   top

Trade secrets and other types of “undisclosed information” which have commercial value must be protected against

breach of confidence and other acts contrary to honest commercial practices. But reasonable steps must have been taken to keep the information secret. Test data submitted to governments in order to obtain marketing approval for new pharmaceutical or agricultural chemicals must also be protected against unfair commercial use.

Curbing anti-competitive licensing contracts back   to   top

The owner of a copyright, patent or other form of intellectual property right can issue a licence for someone else to produce or copy the protected trademark, work, invention, design, etc. The agreement recognizes that the terms of a licensing contract could restrict competition or impede technology transfer. It says that under certain conditions, governments have the right to take action to prevent anti-competitive licensing that abuses intellectual property rights. It also says governments must be prepared to consult each other on controlling anti-competitive licensing.

Enforcement: tough but fair back   to   top

Having intellectual property laws is not enough. They have to be enforced. This is covered in Part 3 of TRIPS. The agreement says governments have to ensure that intellectual property rights can be enforced under their laws, and that the penalties for infringement are tough enough to deter further violations. The procedures must be fair and equitable, and not unnecessarily complicated or costly. They should not entail unreasonable time-limits or unwarranted delays. People involved should be able to ask a court to review an administrative decision or to appeal a lower court’s ruling.

The agreement describes in some detail how enforcement should be handled, including rules for obtaining evidence, provisional measures, injunctions, damages and other penalties. It says courts should have the right, under certain conditions, to order the disposal or destruction of pirated or counterfeit goods. Wilful trademark counterfeiting or copyright piracy on a commercial scale should be criminal offences. Governments should make sure that intellectual property rights owners can receive the assistance of customs authorities to prevent imports of counterfeit and pirated goods.

Technology transfer back   to   top

Developing countries in particular, see technology transfer as part of the bargain in which they have agreed to protect intellectual property rights. The TRIPS Agreement includes a number of provisions on this. For example, it requires developed countries’ governments to provide incentives for their companies to transfer technology to least-developed countries.

Transition arrangements: 1, 5 or 11 years or more back   to   top

When the WTO agreements took effect on 1 January 1995, developed countries were given one year to ensure that their laws and practices conform with the TRIPS agreement. Developing countries and (under certain conditions) transition economies were given five years, until 2000. Least-developed countries had 11 years, until 2006 — now extended to 2013 in general, and to 2016 for pharmaceutical patents and undisclosed information.

If a developing country did not provide product patent protection in a particular area of technology when the TRIPS Agreement became applicable to it (1 January 2000), it had up to five additional years to introduce the protection. But for pharmaceutical and agricultural chemical products, the country had to accept the filing of patent applications from the beginning of the transitional period (i.e. 1 January 1995), though the patent did not need to be granted until the end of this period. If the government allowed the relevant pharmaceutical or agricultural chemical to be marketed during the transition period, it had to — subject to certain conditions — provide an exclusive marketing right for the product for five years, or until a product patent was granted, whichever was shorter.

Subject to certain exceptions, the general rule is that obligations in the agreement apply to intellectual property rights that existed at the end of a country’s transition period as well as to new ones.

NDA means New Drug Application. This application is available at the Food and Drug Administration (FDA).

When the sponsor of a new drug believes that enough evidence on the drug's safety and effectiveness has been obtained to meet the FDA's requirements for marketing approval, the sponsor submits to the FDA a new drug application (NDA).

In other words, when a pharmaceutical company creates a new drug, the company must contact the FDA and demonstrate that the new drug has a particular quality and that the drug is safe and effective. In this case, the pharmaceutical company will have to fill out a new drug application (NDA). If the NDA is approved, then the product may be marketed in the United States.

The application must contain data from specific technical viewpoints for review. The review is a comprehensive analysis of clinical trial data and other information prepared by the FDA drug application reviewers. A review is divided into sections on medical analysis, chemistry, clinical pharmacology, biopharmaceutics, pharmacology, statistics, and microbiology.

For internal tracking purposes, all NDA applications are assigned an NDA number. The NDA number is a six-digit number assigned by the FDA staff to each application for approval to market a new drug in the United States. A drug can have more than one application number if it has different dosage forms or routes of administration.

ANDA means Abbreviated New Drug Application. This application is available at the Food and Drug Administration (FDA).

An abbreviated new drug application (ANDA) contains data that, when submitted to the FDA, provides for the review and ultimate approval of a generic drug product. Generic drug applications are called "abbreviated" because they are not required to include preclinical (animal) and clinical (human) data to establish safety and effectiveness.

Instead, a generic applicant must scientifically demonstrate that its product is bioequivalent (i.e., performs in the same manner as the original drug). Once approved, an applicant may manufacture and market the generic drug product to provide a safe, effective, low cost alternative to the public.

For internal tracking purposes, all ANDA applications are assigned an ANDA number. The ANDA number is a six-digit number assigned by the FDA staff to each application for approval to market a generic drug in the United States.

A generic drug must be the same as the brand-name drug in dosage, safety, strength, how it is taken, quality, performance, and intended use. Before approving a generic drug product, the FDA requires many rigorous tests and procedures to assure that the generic drug can be substituted for the brand-name drug. The FDA bases evaluations of substitutability or "therapeutic equivalence" of generic drugs on scientific evaluations.

SUPAC

The acronym "SUPAC" stands for "Scale-Up and Post-Approval Changes". It refers to the FDA-recommended testing and filing actions to be taken by a pharmaceutical firm when it changes the manufacturing processes of a drug product that has been approved via a New Drug Application (NDA), an Abbreviated New Drug Application (ANDA), or an Abbreviated Antibiotic Drug Application (AADA). The Agency has provided its recommendations to industry in the form of Guidances.

As you may be aware, 21 CFR 314.70 already provides instructions for how changes to approved manufacturing process should be reported to the Agency. Specifically, depending on the magnitude of the change and the possibility that the change could negatively affect the product, the Code provides that notification should be accomplished in one of three ways:

1. Via a supplement that requires approval by the FDA prior to implementation of the change;

2. Via a supplement that does not require approval by the FDA prior to implementation of the change ("changes being effected");

3. Via an annual report.

Unfortunately, the instructions indicating which type of changes fall into what notification category can be broadly interpreted and are sometimes difficult to follow. Luckily, the regulations [21 CFR 314.70(a)] also indicate that less burdensome routes of notification may be followed if those routes are published in the Federal Register (FR). That is the main purpose of the SUPAC Guidances - to provide industry with clear, streamlined (i.e., "less burdensome") ways to test and report manufacturing changes. (Note: As required by 21 CFR 314.70(a), the documents are issued via the FR.)

Why do the SUPAC Guidances offer an advantage over the regulations?

The documents are specific for particular dosage forms. This approach was taken since some product types are more complicated than others, and as such, will likely require more complicated controls. To date, two Guidances have been finalized. They are:

Guidance for Industry: Immediate Release Solid Oral Dosage Forms---Scale-Up and Post-Approval Changes: Chemistry, Manufacturing and Controls, In Vitro Dissolution Testing, and In Vivo Bioequivalence Documentation (November 1995)

Guidance for Industry: Nonsterile Semisolid Dosage Forms---Scale-Up and Post-Approval Changes: Chemistry, Manufacturing and Controls; In Vitro Dissolution Testing and In Vivo Bioequivalence Documentation (May 1997)

In addition, SUPAC documents covering other dosage forms (e.g., extended-release products, transdermals, parenteral solutions), as well as a related document(s) for bulk active substances, are at various stages of development.

The FDA and industry have been working very closely to prepare these documents. Industry supplies its input at meetings and workshops as well as through written comments.

Although these SUPAC documents are not regulations, the FDA is working to ensure that the Guidances are as consistently interpreted and applied by both the Agency and industry as possible. To this end, the Agency has undertaken a rather comprehensive training program, providing in-house training for its personnel and public workshops for others. Furthermore, although the main thrust of the training is provided at the time a Guidance is issued, the Agency has been diligent in ensuring that subsequent, ongoing

interpretation and application of the recommendations remain consistent. In fact, as recent as February 1997, the FDA issued two documents discussing how to properly utilize the SUPAC-IR Guidance for Industry (issued November 1995). These documents are:

Manufacturing Equipment Addendum to the Guidance for Industry for Scale-Up and Post Approval Changes: Immediate Release Products (SUPAC-IR), Draft Guidance for Industry. Released on February 3, 1997.

Letter to industry from Dr. Roger L. Williams, Deputy Center Director for Pharmaceutical Science, CDER, dated February 18, 1997. This letter discussed how industry should interpret stand alone packaging operation site changes and stand alone analytical site changes based upon the Agency's re-assessment of these issues. In addition, it provided the answers to significant questions frequently asked by industry.

Finally, you asked how these Guidances affect you and your company, specifically. That depends on what types of products you manufacture, and your job responsibilities in the company. If you are involved in regulatory affairs submission work, scale-up activities, process validation, or analytical testing, you may be affected, assuming your company manufactures immediate release oral dosage forms and nonsterile semisolid dosage forms. (As indicated above, only these two types of products are currently covered by SUPAC Guidances.) If you manufacture another product type, SUPAC won't affect you now; your company must still interpret and follow 21 CFR 314.70. But even if that is the case, keep an eye out for future SUPAC Guidances that could affect your product -- they may be coming soon.

The Common Technical DocumentThe agreement to assemble all the Quality, Safety and Efficacy information in a common format (called CTD - Common Technical Document ) has revolutionised the regulatory review processes, led to harmonised electronic submission that, in turn, enabled implementation of good review practices. For industries, it has eliminated the need to reformat the information for submission to the different ICH regulatory authorities.

The CTD is organised into five modules. Module 1 is region specific and Modules 2, 3, 4 and 5 are intended to be common for all regions. In July 2003, the CTD became the mandatory format for new drug applications in the EU and Japan, and the strongly recommended format of choice for NDAs submitted to the FDA.

he government on Thursday notified the new drug policy that aims at bringing more medicines under price control.

The National Pharmaceutical Pricing Policy (NPPP) 2012, which was cleared by the government in November, would bring 348 essential drugs under price control.

"The NPPP-2012 approved by the Cabinet on November 22 , 2012 has been notified on December 7, 2012," Minister of State for Chemicals and Fertilisers Srikant Kumar Jena said in a written reply in Lok Sabha.

The outgoing drug policy of 1994, which covers 74 bulk drugs, was implemented through Drugs Price Control Order (DPCO) 1995.

"Based on the same, a new DPCO (Drugs Price Control Order) shall be prepared, notified," he added.

Price control over drugs was first introduced in the country in the aftermath of the Chinese aggression by Drugs (Display of Prices) Order 1962 and the Drugs (Control of Prices) Order 1963.

In another reply, Jena said the National Pharmaceuticals Pricing Authority (NPPA) has requested the Department of Pharmaceuticals for amendment in 'form IV' of DPCO, 1995, "which will enable them to seek additional information from the importers of drugs than what is prescribed under DPCO, 1995."

In an earlier post (here) we had blogged about the National Pharmaceutical Policy 2011 and its essential features.  The last post left off at AIDAN’s (All India Drug Action Network) PIL (Public Interest Litigation) and the Supreme Court’s (SC) observations that the government should ensure that the prices of essential drugs reduce rather than escalate.  During the hearing of this PIL the SC recently directed the Government to expedite the notification of the policy. It was notified on 7 December 2012. The full policy can be found here.

The National Pharmaceuticals Pricing Policy, 2012 will replace the Drug Policy of 1994 and is intended to be a continuation of the 1994 Policy.

Key points in the policy are:

The ceiling price of drugs will be fixed by adopting simple average price of all brands having a market share more than or equal to 1% of the total market turnover of that medicine. The ceiling price would be fixed on the basis of dosage per tablet, capsule standard injection volume. This approach is different from the weighted average price of top brands which was a severely criticised feature of the earlier policy. Experts believed that the weighted average calculation method would have driven up prices of essential drugs rather than reduced them.

Imported drugs have been brought within the purview of the policy for the first time.

Drugs patented under the Indian Patents Act, 1970 and which have been made as a result of indigenous products or process have been exempted from price control for a period of five years. Further, a formulation involving a new delivery system developed through indigenous R&D would be eligible for exemption from price control for a period of 5 years from the date of its market approval in India.  This could mean that some essential medicines will be kept outside the ambit of price control. However on the face of it, it seems to have been brought in to incentivise investment by pharma companies.

One of the fears was that since the new policy introduces price controls at the formulation stage manufactures could easily bypass price control by combining the essential drug with another drug or a non-essential drug however the policy addresses this problem by stating that in such cases manufacturers shall be required to seek price approval from the Government before launching the new drug.

Prices of non price control drugs will also be regulated to a certain extent, the policy states that the Government will ensure that their prices are not raised by more than 10% in a year.

There is still no final decision of the status of patented drugs. Their prices will be decided by a separate committee.

Reaction from the Industry

The policy seems to have been received with mixed feelings. Neither the industry not the activists seem completely happy with it. 

Most feel that the recent changes to the calculation of prices will definitely bring down prices of drugs but will severely hit the larger players (who may have to take a hit of about 15%-20% in revenues) in the market which could in turn effect investment in the sector. (However in this article available on Pharmabiz here, P.A.Francis argues why he thinks this is an industry friendly policy after all).

One view from the industry seems quite favourable to the policy, Shakti Chakraborthy, the President of Lupin Ltd Group while commenting on the policy stated, “It is a good thing that the government has chosen to adopt a market-based mechanism as against a cost-based mechanism, thus protecting industry interest to a large extent as also ensuring that drugs reach patients in a cost-effective manner."

The main bone of contention for the activists seems to be the government’s decision to opt for market based pricing rather than cost based pricing. They feel that this method will almost certainly lead to an overall rise in prices.

The SC is expected to examine the policy and hear further contentions based on AIDAN’s PIL in the second week of January. This seems to be a policy whose full effects will probably be clear only once it is implemented.

HISTORY OF ICH

The Need to HarmoniseThe realisation that it was important to have an independent evaluation of medicinal products before they are allowed on the market was reached at different times in different regions. However in many cases the realisation was driven by tragedies, such as that with thalidomide in Europe in the 1960s.

For most countries, whether or not they had initiated product registration controls earlier, the 1960s and 1970s saw a rapid increase in laws, regulations and guidelines for reporting and evaluating the data on safety, quality and efficacy of new medicinal products. The industry, at the time, was becoming more international and seeking new global markets, however the divergence in technical requirements from country to country was such that industry found it necessary to duplicate many time-consuming and expensive test procedures, in order to market new products, internationally.

The urgent need to rationalise and harmonise regulation was impelled by concerns over rising costs of health care, escalation of the cost of R&D and the need to meet the public expectation that there should be a minimum of delay in making safe and efficacious new treatments available to patients in need.

Initiation of ICHHarmonisation of regulatory requirements was pioneered by the European Community (EC), in the 1980s, as the EC (now the European Union) moved towards the development of a single market for pharmaceuticals. The success achieved in Europe demonstrated that harmonisation was feasible. At the same time there were bilateral discussions between Europe, Japan and the US on possibilities for harmonisation. It was, however, at the WHO Conference of Drug Regulatory Authorities (ICDRA), in Paris, in 1989, that specific plans for action began to materialise. Soon afterwards, the authorities approached IFPMA to

discuss a joint regulatory-industry initiative on international harmonisation, and ICH was conceived.

The birth of ICH took place at a meeting in April 1990, hosted by EFPIA in Brussels. Representatives of the regulatory agencies and industry associations of Europe, Japan and the US met, primarily, to plan an International Conference but the meeting also discussed the wider implications and terms of reference of ICH.

At the first ICH Steering Committee (SC) meeting of ICH the Terms of Reference were agreed and it was decided that the Topics selected for harmonisation would be divided into Safety, Quality and Efficacy to reflect the three criteria which are the basis for approving and

authorising new medicinal products.

The Evolution of ICHFor two decades the ICH process has achieved much success. This success is attributed not only to a process of scientific consensus developed between industry and regulatory experts, but also to the commitment of the regulatory parties to implement the ICH Tripartite Harmonised Guidelines and recommendations.

Since ICH's inception in 1990, the ICH process has gradually evolved. ICH's first decade saw significant progress in the development of Tripartite ICH Guidelines on Safety, Quality and Efficacy topics. Work was also undertaken on a number of important multidisciplinary topics, which included MedDRA (Medical Dictionary for Regulatory Activities) and the CTD (Common Technical Document). As ICH started into a new millennium, the need to expand communication and dissemination of information on ICH Guidelines with non-ICH regions became a key focus. Attention was also directed towards facilitating the implementation of ICH Guidelines in ICH's own regions.

Throughout the second decade the development of ICH Guidelines continued, but with more attention given to the need to maintain already existing Guidelines as science and technology continued to evolve. The need to leverage with other organisations was also acknowledged, particularly for the development of electronic standards. The SC recognised the benefits afforded by collaboration with Standards Development Organisations, not only from the perspective of having a larger available pool of technical expertise, but also the opportunity to progress ICH standards as global standards.

Entering into its third decade of activity, ICH's attention is directed towards extending the benefits of harmonisation beyond the ICH regions. Training, as well as active participation of non-ICH regions in guideline development, are seen as key in this effort.

Guidelines

The ICH topics are divided into four categories and ICH topic codes are assigned according to these categories.

Quality Guidelines

Harmonisation achievements in the Quality area include pivotal milestones such as the conduct of stability studies, defining relevant thresholds for impurities testing and a more flexible approach to pharmaceutical quality based on Good Manufacturing Practice (GMP) risk management.

Safety Guidelines

ICH has produced a comprehensive set of safety Guidelines to uncover potential risks like carcinogenicity, genotoxicity and reprotoxicity. A recent breakthrough has been a non-clinical testing strategy for assessing the QT interval prolongation liability: the single most important cause of drug withdrawals in recent years.

Efficacy Guidelines

The work carried out by ICH under the Efficacy heading is concerned with the design, conduct, safety and reporting of clinical trials. It also covers novel types of medicines derived from biotechnological processes and the use of pharmacogenetics/genomics techniques to produce better targeted medicines.

Multidisciplinary Guidelines

Those are the cross-cutting topics which do not fit uniquely into one of the Quality, Safety and Efficacy categories. It includes the ICH medical terminology (MedDRA), the Common Technical Document (CTD) and the development of Electronic Standards for the Transfer of Regulatory Information (ESTRI).

New Codification as per November 2005In November 2005, the ICH Steering Committee adopted a new codification system for ICH Guidelines. The purpose of this new codification is to ensure that the numbering / coding of ICH Guidelines is more logical, consistent and clear. Because the new system applies to existing as well as new ICH Guidelines a history box has been added to the beginning of all Guidelines to explain how the Guideline was developed and what is the latest version.

With the new codification revisions to an ICH Guideline are shown as (R1), (R2), (R3) depending on the number of revisions. Annexes or Addenda to Guidelines have now been incorporated into the core Guidelines and are indicated as revisions to the core Guideline (e.g., R1).

For implementation reasons, the Regulatory Authorities working within the ICH Regions (European Commission, Food and Drug Administration and Ministry of Health, Labor and Welfare) may not change the codification retrospectively.

U.S. FDA Drug Establishment Registration and Listing RequirementsOwners or operators of all drug establishments, not exempt under section 510(g) of the Food, Drug, and Cosmetic Act (Act), that engage in the manufacture, preparation, propagation, compounding, or processing of a drug or drugs shall register and submit a list of every drug in commercial distribution.

Manufacturing or processing means the manufacture, preparation, propagation, compounding, or processing of a drug or drugs as used in section 510 of the Act and is the making by chemical, physical, biological, or other procedures of any articles that meet the definition of drugs in section 201(g) of the Act. The term includes manipulation, sampling, testing, or control procedures applied to the final product or to any part of the process.

The term "drug" means (A) articles recognized in the official United States Pharmacopoeia, official Homoeopathic Pharmacopoeia of the United States, or official National Formulary, or any supplement to any of them; and (B) articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals; and (C) articles (other than food) intended to affect the structure or any function of the body of man or other animals; and (D) articles intended for use as a component of any article specified in clause (A), (B), or (C).

Registrar Corp helps businesses comply with U.S. FDA Drug registration and listing

requirements. For U.S. FDA Drug assistance, simply click the U.S. FDA Drug category applicable to your drug products.

Active Pharmaceutical Ingredient (API) Registration API Examples

Drug Certificates Issued By Registrar Corp

An Active Pharmaceutical Ingredient is any substance or mixture of substances indended to be used in the manufacture of a drug (medicinal) product and that, when used in the production of a drug, becomes an active ingredient of the drug product. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affec the structure or function of the body. For assistance with U.S. FDA Active Pharmaceutical Ingredient registration and listing requirements, simply click the Active Pharmaceutical Ingredient Certificate shown on the left.

Drug Intermediates Establishment Registration

Drug Certificates Issued By Registrar Corp

Drug Intermediates are materials produced during the steps in the synthesis of an Active Pharmaceutical Ingredient (API) that must undergo further molecular change or processing before becoming an API. For assistance with U.S. FDA Drug Intermediate registration and listing requirements, simply click the Drug Intermediate Certificate shown on the left.

Prescription Drug Establishment Registration

Drug Certificates Issued By Registrar Corp

A Prescription Drug is a human drug that is not safe for use except under the supervision of licensed medical practitioner. For assistance with U.S. FDA Prescription Drug registration and listing requirements, simply click the Prescription Drug Certificate shown on the left.

Over the Counter Drug (OTC) Establishment Registration

Drug Certificates Issued By Registrar Corp

An Over-the-Counter Drug is a human drug that is safe and effective for use without prescription by a licensed medical practitioner. For assistance with U.S. FDA Over-the-Counter Drug registration and listing requirements, simply click the Over-the-Counter Drug Certificate shown on the left.