Every 2 months.

Various sources, but primarily Mosby’s drug consult (brand names) and EMTREE (chemical names).

Not yet.

No, but we would certainly accept any recommendations from our users and take them under serious consideration.

No. The thesaurus is not available as a separate source.

This is the standard, in these cases, used by the ICH in creating MedDRA. In these cases we have included the US spelling as synonyms.

This is an older term used by the RTECS database, usually referring to sheep or goats.

Synonyms are treated with equal weight.

Yes.

RTECS terms have been mapped to the proper term and level of the MedDRA hierarchy, and then these RTECS terms are added to the Thesaurus as synonyms to these MedDRA terms. Where there are RTCS terms that cannot be mapped, specific entries were added to the hierarchy.

We needed a strict hierarchical view for adverse effects/toxicities and drug names and needed a comprehensive dictionary of terms from which to build our thesaurus. We chose what we felt were standards in this area (see previous question for details).

We created the Thesaurus. The thesaurus we use in PharmaPendium is based on well known building blocks (FDA Approval Packages, Mosby’s, MedDRA, and RTECS) with additions based on content in the product when needed.

• For drug names, we use a drug thesaurus from Mosby’s Drug Consult and added some synonyms from EMTREE when needed.
• For adverse effects/toxicities, we use a thesaurus based on MedDRA (by ICH) with terms from FDA documents, Meyler’s, Mosby’s Drug Consult and RTECS mapped into the MedDRA hierarchy.

• Drug names (generic and brand names, chemical names)
• Adverse effects/toxicities

When using the quick search or advanced text search synonyms can be switched on or off. When searching within a document of the individual content sources or when searching within a browse tree the synonyms are automatically included.

Metabolite information extracted from the literature, including the transformations shown is integrated with the parental structure.

PharmaPendium uses Mosby’s Drug Consult class definitions. Mosby’s uses FDA classifications.

Pharmapendium does not have target information on every drug yet, but claims to have every target for every drug. This is an ongoing process and approximately 2000 new drug/target relationships have already been added.

PharmaPendium target information and the relationship between targets and drugs, comes from xPharm, drug labels, and FDA Approval Packages. PharmaPendium understands that this is a crucial content area in the product, and is committed to adding the target/drug associations and target synonym list to the target list.

PharmaPendium contains 149 targets and links 450 drugs to those targets. Most targets have ‘Information Pages’ containing Adverse Effect/Toxicity tables on drugs known to interact with those targets, and xPharm target profiles.

In some cases, it is simply because we have no data in that category. For example, there are some effects that are specific to animal testing which would not appear in the other categories, and some drugs may be approved only in Europe, and thus would not be listed in the USFDA’s AERS database of post market reports. Some cases include drugs for which we have not yet been able to obtain data in a certain category due to, for example, a missing original approval package (most preclinical data, for example, is listed in the ‘Originator’ Approval Package listed in our system as “S-000”; if we do not have that document, the preclinical data for that drug may be limited to extracted journal data and data contained on the package insert).

Pharmacokinetics/pharmacodynamics information is not extracted at this time. However, the FDA Approval Packages found in PharmaPendium are an incredibly powerful source of human and animal PK/PD data (Tmax, Cmax, T1/2, plasma concentration/time curves, etc.). Much of these data cannot be found in any other commercial source.

This category is not extracted, however this data can be found searching the FDA Approval Packages, Package Inserts (Labels), and Meyler’s sources. We have added all relevant (for approved drugs) Mutagenicity data from RTECS, it can be found as a node on the AE/Tox tree.

MedDRA, a thesaurus published by the ICH and RTECS ® were used:

• RTECS terms have been mapped to the proper term and level of the MedDRA hierarchy, and then these RTECS terms are added to the Thesaurus as synonyms to these MedDRA terms. When there are RTECS terms that cannot be mapped, specific entries are added to the hierarchy.
• Extracted preclinical (animal) and clinical data and (post-market) AERS records extracted from the sources in PharmaPendium (for example the FDA Approval Packages, Meyler’s) were mapped to this thesaurus.
• This allowed the PharmaPendium interface to provide a longitudinal view from preclinical (animal), to clinical to post-market data.

PharmaPendium is designed to provide its users with a “longitudinal” view of preclinical, clinical, and post market data, which are filtered by user-defined parameters (target, class, chemistry, adverse effects). As a user looks at a particular drug’s data view they can toggle between observed animal effects, clinically-observed effects, and post market reports. This allows a research thread that examines how animal effects correlated to clinical (human) effects, and finally to the general population (post market).

This is the only content offering that makes such a research thread possible, allowing further investigation on the predictability of certain animal studies, species-specific effects, etc.

No, we do not extract this data. However, users can search PharmaPendium for particular excipients as FDA Approval Packages often contain excipients used and related safety concerns.

Not at the moment but we are gathering information from customers on what data they would like to see added.

RTECS data relating to the approved drugs contained in PharmaPendium are included. However, certain RTECS records relating to in vitro studies are not included.

The extracted journal data from RTECS and MDL Metabolite goes back 20 years and sometimes beyond. It’s important to remember that we only use extracted data for the PharmaPendium drug list, so these journal extract date ranges will reflect the approval dates of each drug.

New journal extracted data is added quarterly, however it might take several months to extract that data since this is done manually and requires careful processing and quality control. Therefore it might be 6-12 months after a journal article gets published before it becomes available in PharmaPendium.

Yes.

Some cited toxicity data in Pharmapendium has been extracted from a pool of over 3000 journals and other worldwide sources. This is the same group of sources used to build the RTECS® (Registry of Toxic Effects of Chemical Substances) database.

This product includes only extracted data and citations on approved drugs, matching the other content in the product. Extracted information includes drug name, species, dose, dose type, toxicity and citation.

We extracted the following data on approved drugs:

• Preclinical data extracted from the literature (from RTECS)
• Metabolite data extracted from journals for approved drugs.

We DON’T have:

AERS took over for the older system “SRS” (safety reporting system) in October 1997 and our system matches this.

An important fact about AERS is that nothing gets deleted, so withdrawn drugs, etc. never leave the database.

This has more to do with the outcome than the adverse event. Definition of serious (FDA): Death, Life-threatening, Hospitalization (initial or prolonged), Persistent or Significant Disability, Congenital Anomaly, Important Medical Events that may jeopardize the patient and may require medical or surgical intervention to prevent one of the previously-listed outcomes.

Yes.

Yes.

Meyler’s covers 1872 drugs in Pharmapendium. Most overlap with the FDA, since even though Meyler’s is more of a European source, it also covers drugs not approved in the US. It also covers some other areas such as ‘drugs of abuse’ on which our customers have commented positively. Meyler’s has an editorial board that decides which drugs/papers are included in each installment.

Meyler’s as a source is available both in its original form (like an online book), and through extracted data available in the PharmaPendium clinical view. A user can search Meyler’s together with the other PharmaPendium sources through the Quick search feature, or they can open the Meyler’s source and search it by itself. This source also has a linked table of contents for easy browsing.

No, Meyler’s covers many drugs that were only approved outside the US.

Basically yes. PDR information is given by the Drug Company itself, whereas Mosby’s Drug Consult data (used in PharmaPendium) is taken from the FDA-approved label. However these sources are quite similar in the information provided.

Yes.

No.

This is not a particular feature of PharmaPendium, but users can examine label histories by looking at various dated labels in the FDA Approval Package.

History can also be studied by examining the Correspondence and letters sections, which frequently contain interactions between the company and the FDA regarding label changes.

• PharmaPendium has coverage on approx. 120 vitamins and minerals.
• We do not cover drugs for animals. The FDA's Center for Veterinary Medicine is responsible for the agency's overview of these products.
• Over-the-counter products that are approved for marketing through a process other than submitting a New Drug Application are not included.
• Prescription drugs sold in countries other than the United States are included. Meyler’s side Effects of Drugs source provides substantial coverage for drugs in this category.
• Drugs which are under review at FDA and for which no action regarding approval has occurred are not covered. Most of this information is proprietary.

These are usually argued by the company to be trade secrets or similar. Most of these can be found in chemistry reviews. After approval, the company and FDA will decide together which information is public, and which is proprietary. This can be a long process, which is why an FDA Approval Package is typically not available until many months after a drug is approved.

FDA Approval Packages are basically the ‘argument’ made for approval, or approval with conditions. To this end, pivotal (decision-critical) studies are contained in these packages. Appendices are sometimes used in special cases for various reasons, and are included in the documents. Conditions, such as “Phase IV Commitments” are also included.

Mosby’s Drug Consult is the PharmaPendium source for the current label used in the US. This source is updated every 2 months.
 
FDA Approval Packages are not a good source for current labels, as these documents go through a rigorous screening process by the FDA Freedom of Information office (FOI) and are thus less-than-current when they are made available.
 
When any new approval document (including labels) is made available we add it to the drug’s FDA Approval Package section. This gives the user the advantage of looking at the various changes made to labels on drugs over the years, by selecting approval package labels by date.

Yes, when available, any letter associated with the approval/withdrawal of a drug is included. These are mostly found in the “correspondence” sections of the FDA Approval Packages.

Yes.

Yes, in many cases this information is noted in the FDA Approval Package reviews and correspondence documents.

According to the FDA/CDER website:

The FDA/CDER website has various FDA Approval package documents available online for download. PharmaPendium covers all drugs on this site and all updates made to this site up to Sept 2005. Updates and new documents added to this site are current through Sept 2005 - this gap was necessary to finish building or launching the product and will be brought up to date within 3 months of release. PharmaPendium also provides FDA Approval Package documents for nearly 200 drugs NOT included on the FDA/CDER site.

IMPORTANT: FDA/CDER site only provides image files for download. These are not searchable, and data has not been extracted as it has been in PharmaPendium. This is a major distinction and a major value that PharmaPendium provides to its customers.

• Medical/Clinical Review
• Chemistry Review
• Pharmacology Review
• Toxicology Review
• Microbiology Review
• Clinical Pharmacology & Biopharmaceutical Review
• Statistical Review
• Bioequivalence Review
• Correspondence
• Approval letters
• Warning Letters
• Labels

The FDA creates the packages which consist of various reviews. The FDA Reviewer includes selected research data provided by the sponsor and includes comments on that data in the review documents. The package also includes correspondence which is sometimes created by the sponsor and sometimes by the FDA.

Not all drugs in PharmaPendium have associated structures. In the case of biologics and mixtures, where the active ingredients are listed in separate entries, they do not have structures. Most other drugs, with very few exceptions are searchable by chemical structure.

No. Pharmapendium currently does not cover non-approved drugs – but we do cover some drugs that were approved and then withdrawn. One of the sources Pharmapendium is considering is the FDA Advisory committee meeting minutes and material.

On June 30, 2003, FDA transferred some of the therapeutic biological products that had been reviewed and regulated by the Center for Biologics Evaluation and Research (CBER) to the Center for Drug Evaluation and Research (CDER).

Categories of Therapeutic Biological Products Transferred to CDER

• Monoclonal antibodies for in vivo use.
• Proteins intended for therapeutic use, including cytokines (e.g. interferons), enzymes (e.g. thrombolytics), and other novel proteins, except for those that are specifically assigned to CBER (e.g., vaccines and blood products). This category includes therapeutic proteins derived from plants, animals, or microorganisms, and recombinant versions of these products.
• Immunomodulators (non-vaccine and non-allergenic products intended to treat disease by inhibiting or modifying a pre-existing immune response).
• Growth factors, cytokines, and monoclonal antibodies intended to mobilize, stimulate, decrease or otherwise alter the production of hematopoietic cells in vivo.

Categories of Therapeutic Biological Products Remaining in CBER

• Cellular products, including products composed of human, bacterial or animal cells (such as pancreatic islet cells for transplantation), or from physical parts of those cells (such as whole cells, cell fragments, or other components intended for use as preventative or therapeutic vaccines).
• Gene therapy products. Human gene therapy/gene transfer is the administration of nucleic acids, viruses, or genetically engineered microorganisms that mediate their effect by transcription and/or translation of the transferred genetic material, and/or by integrating into the host genome. Cells may be modified in these ways ex vivo for subsequent administration to the recipient, or altered in vivo by gene therapy products administered directly to the recipient.
• Vaccines (products intended to induce or increase an antigen specific immune response for prophylactic or therapeutic immunization, regardless of the composition or method of manufacture).
• Allergenic extracts used for the diagnosis and treatment of allergic diseases and allergen patch tests.
• Antitoxins, antivenins, and venoms.
• Blood, blood components, plasma derived products (for example, albumin, immunoglobulins, clotting factors, fibrin sealants, proteinase inhibitors), including recombinant and transgenic versions of plasma derivatives, (for example clotting factors), blood substitutes, plasma volume expanders, human or animal polyclonal antibody preparations including radiolabeled or conjugated forms, and certain fibrinolytics such as plasma-derived plasmin, and red cell reagents.

PharmaPendium covers biologics products that are regulated by CDER now. For more information, check out the following FDA site: http://www.fda.gov/cber/transfer/transfer.htm

European Medicines Agency's (EMEA) European Public Assessment Reports (EPARs) is covered with 80,000 pages of searchable EPAR documents on EMEA-approved drugs, including over 50 drugs/mixtures not approved by the FDA.
The Meyler’s Side Effects of Drugs and our extracted Toxicity data from journals (RTECS) sources cover most drugs approved only in Europe. We do not know if all drugs in this category are covered.

PharmaPendium, through its various sources has coverage on most drugs withdrawn over the past ten years.

Content Updates occur every 2 months and includes any source updates that fall into that timing:

• FDA docs: every update
• Meyler’s: 1 update/year
• RTECS: Quarterly
• Metabolite: Quarterly
• Mosby’s: none – to be updated with Daily Med Lables starting 10/2007
• AERS: Quarterly, but usually provided ~6 months late by FDA

PharmaPendium covers over 4000 drugs for all sources, this number increases with each new update.

• FDA Approval Packages: 1443, 857 that are considered ‘full’ (including pharmacology, medical and chemistry reviews, etc.) and are mostly 1992 – present. There are also approximately 700 considered ‘partial’, which tend to be drugs approved prior to 1992 and for which we do not have the full list of FDA reviews. For these packages, we will often have the various approved labels, approval letters, and company-FDA correspondence.
• Mosby’s Drug Consult (Package Inserts; “labels”): Covers 1751 drugs (US Approved). Most of which overlap with our FDA Approval Package coverage. This also includes drugs discontinued post-1997 (79 drugs). Mosby’s has been discontinued and will no longer be updated. The type of content found in Mosby’s will be replaced by updating with DailyMed labels, started in Oct 2007.
• Meyler’s Side Effects of Drugs: Covers US–approved drugs, in addition hundreds of drugs approved only outside the US are included.
• AERS (our post-market data: Covers all US-approved drugs on the market. Drugs which have been discontinued or withdrawn are not deleted. AERS (Adverse Event Reporting System database) has been online since 1998, replacing the older SRS. So some older, withdrawn drugs will not be in the AERS database.

Search all FDA documents dating back to 1938 and benefit from PharmaPendium’s unique features and functionality allowing you to:

• Make highly confident drug development decisions.
• Evaluate relevant data in a regulatory, scientific and commercial context.
• Learn from past submission mistakes.
• Improve your workflow through the fast and accurate retrieval of all relevant data.
• Track pharmacological effects at every phase of development.
• Prioritize the safest and most promising candidates for further investment.
• Gain and maintain market position.
• Present the most compelling regulatory case.
• Shape your experimental designs.
• Re-examine biological data spanning over 60 years for the first time.
• Mine a wealth of historic biology data and make new discoveries that may otherwise go unfound.

• Drug safety researchers
• Toxicologists
• Safety pharmacologists
• Regulatory affairs
• Information specialists
• DMPK/ADME
• Clinical researchers
• Pharmacovigilance

The only online resource able to search all FDA/CDER/FOI archived FDA drug approval review and correspondence documentation since 1938, as well as an EMEA EPAR approval document database, PharmaPendium gives you unrivalled insights into the entire history of drug development. Please refer to ‘What is Pharmapendium’ for more information.

Please visit our news release section on a regular basis to keep up to date.

Yes, PharmaPendium links to the original literature. If you have access rights to those literature sources, you should be able to get the original publication.

Yes, structures are exported as Chime strings in Excel export when “View Chemical Structures” feature is turned ON.

Yes, if you have downloaded the MDL Draw plug-in. Click the structure to bring up the chemical search page, then double-click to open MDL Draw (structure automatically loaded, then save.

Other option: Export the result with “View Chemical Structures” feature turned ON.

Yes.

Not SD Files, but Structure information and adverse effect/toxicity data will be exportable together in a tab-separated file that can be directly exported into ISIS for Excel.

There is no specific reporting tool. We do have ‘printer-friendly’ pages, particularly in areas where printing will be common.

“Investigations” is a significant section of this hierarchy. It contains investigation results that may lead to a diagnosis of the disorders found elsewhere on the list, but are independently listed. For instance “Electrocardiogram QT prolonged” (an investigation result) may be a sign of “Torsade de Pointes”, a cardiac disorder, but both are listed independently.

Thus, it is important to point out to researchers that they may want to include INVESTIGATION types in their search as well as DISORDERS for a more complete result.

AERS (Adverse Event Reporting System) is not text-searchable, but available through all browse functions and chemical searches. This is for a couple of reasons: it’s a much larger and ‘noisier’ data source than the experimental data we have from preclinical and clinical sources and thus would make hits from other sources more difficult to find in result sets, and the main data type is ‘frequency’ of events, making it difficult to show together with the other data types in the general search. We welcome suggestions on how to make this easier/better.

When searching an FDA Approval Package, you are searching all of the documents that make up that package. Here is a list of the document types: Medical/Clinical Review, Chemistry Review, Pharmacology Review, Toxicology Review, Microbiology Review, Clinical Pharmacology & Biopharmaceutical Review, Statistical Review, Bioequivalence Review, Correspondence, Approval letters, Warning Letters, and Labels.

No – if you have the plug-in installed, then you can cut/paste a structure to Pharmapendium query from your ISIS draw.

Yes – if you use the thesaurus this should work.

Mol file.

You can perform a compound structure AND text search in that search area. Thus one may set up a chemical structure search and enter a target (or other) into the text search box on the form. The result of search a search would be all drugs with X% similarity (for example) to the query structure that also have documents associated with them containing the text search term.

Many are mixtures with >1 active ingredient will not have structure files associated with them. The active ingredients are almost always included with structures by themselves through other drug products. Also, in many cases >1 label will point to the same structure.

This is done using a similarity algorithm using Symyx structural ‘keys’ as variables.

A compound/structure is said to be similar if certain parts of the structure may be replaced and the new structure's behavior is close to the starting structure. Chemical structure searching tools use different techniques to identifying a similar structures and the below information is meant to help you understanding of the method and its limitations.

Structure Similarity Searching in PharmaPendium:

The chemical structures of Drug compounds are registered by Elsevier MDL as so called 'keys'. Each key represents one of the following:

• Structural feature, e.g. a chlorine atom
• Six membered ring
• Combination of rings or other functional groups
• Part of a graph represented in that particular structure (sometimes structures are represented in a mathematical way as graphs)

The entire structure can be represented by a set of keys (Elsevier MDL has identified up to 960 structural keys) which serve as a bitmap or a fingerprint of the structure.

When a similarity search is performed the system translates the query structure into keys and compares this set of keys with the keys’ sets of those structures stored in the database. A structure in the database is notified as a hit if the comparison delivers more (or equal) identity as given by the % range in the query. For example, if you ask for 80% similarity, 80% or more of all keys of the query structure and the selected structure in the database have to be identical to mark the structure in the database as a hit.

While some of the keys describe very common structural entities like a Benzene ring others handle rare occurrences like the CN group. To make the similarity searches more efficient, Elsevier MDL put a weighting over the keys to reflect the occurrence frequency of each key. The weighting is developed out of Elsevier MDL’s Available Chemical Dictionary database (ACD), which contains several hundred thousands of chemical structures. Key comparison and key weighting together make the Elsevier MDL similarity search to a useful tool to identify chemical structures with a high probability of similar properties.

But nevertheless it is important to realize that although a structure might be similar based on the number of similar (chemical) keys, it doesn't mean that the biologically activity is the same since this depends on whether the keys that are found in the similar structures not only reflect the chemical properties but are related to the biological activity as well.

In general it is recommended to not lower the similarity search below 70%.

Literature for Elsevier MDL keys: Re-optimization of MDL Keys for Use in Drug Discovery, Joseph L. Durant,* Burton A. Leland, Douglas R. Henry and James G. Nourse, MDL Information Systems

With the MDL Draw program downloaded and installed you can:

• Load a structure
• Edit a structure
• Similarity/Substructure/Exact Match search

Without MDL Draw you can:

Similarity/Exact Match search for structures found within the system (when selecting “View Chemical Structures”) by clicking on the structures.

The search is a direct filtering of the extracted data database, rather than a search of all of the text. This is a particularly powerful search type, as it can be explicit as to “show me (these) drugs that exhibit (these) effects in (these) species.
(The extracted data search covers preclinical and clinical data but not post-market data. This is due to the different (non-experimental) nature of the post-market AERS data.

No.

Yes, you can do that by clicking on the link ‘query details’ and editing the information.

Yes – if no results are found from your search term, the product will provide a term that “sounds like” the term typed as an option.

Dose data is shown in the units as they exist in the original source, these are not normalized. Single vs. repeated dose are distinguished, and Route of Administration is included where available in the source data.

Not with version one.

No.

Yes.

MDL ISIS for Excel is currently required to view chemical structures. However, PharmaPendium is going to provide other options on chemistry files by the end of 2008.

Yes, since this is an MDL product the data is exportable to ISIS for Excel.

Yes.

Yes.

No.

Oracle relevance scoring is used. A full description of this scoring can be found by clicking here.

Yes.

Search all for “biomarker” and/or “expression” in FDA Approval Packages for your drug class.

• Filter by similarity of choice (Target, Class, chemistry)
• Filter Preclinical by species
• View FDA Approval Package full experiments for observations of interest by clicking on the specific FDA Approval Package link in the data table.

Perform Quick Search for “Phase IV Commitments”.

• Browse into Class of interest.
• View individual Reviews found in FDA Approval Packages for each drug in the class (or an example drug).
• Search for pharmacokinetics/pharmacodynamics data using the “Search this FDA Package” search box.

Select the Target from the Target Browse tree and click on “Clinical data View All”.

• Structural Query (SAR): Find all compounds in the system that have 80% structural similarity to my compound. (You can use a system compound if you do not wish to load one in).
• Sort on Toxicity/Adverse Effect and look for a specific effect in Preclinical Data table.
• Toggle to Clinical Data Table: Do these same drugs show similar clinical effects?
• Click on the Drug Info links of the most similar drugs: Do these compounds interact with the same targets/target families?
• View the 2 most similar compounds that also show similar effect observations: Click on Drug Info to view the individual Drug Information Pages. View the known metabolites for each drug, for the species that shows that effect.

• Type [Drug Class] AND Liver into Quick Search
• Browse by Drug, select Class, in summary table select any liver effect or select View All and sort resulting table.
• Toggle tabular results by Preclinical Data/Clinical data and compare.
• Choose a particular observation on a particular drug and view it in the context of its original document.
• Toggle to Post Market Reports tab to view possible newly reported liver adverse effects.

You can start with a specific side effect and view all drugs that have shown that effect in preclinical, clinical, and clinical studies. You will also be able to view properties such as chemical structure, target, and drug class. This information is designed to help understand other drugs with the same properties that may be likely to show the same effect(s).

Yes.

PharmaPendium is designed to provide its users with views of preclinical, clinical, and post market data that are filtered by user-defined parameters (target, class, chemistry, adverse effects). As a user looks at a particular Drug’s data view they can toggle between observed animal effects, clinically-observed effects, and post market reports. This allows a research thread that examines how animal effects correlated to clinical (human) effects, and finally to the general population (post market). This is the only content offering that makes such a research thread possible, allowing further investigation on the predictability of certain animal studies, species-specific effects, etc.

Yes. Perform a similarity search, then click on the post Market reports tab to view the AERS data associated with the chemical structure search result. This is also possible using a substructure search (or scaffold).

PharmaPendium is the only product which provides these possibilities to filter AERS.

AERS is presented in PharmaPendium in its entirety. We indexed the chemical structures (where available), targets, classes, and adverse effects to the drug compound, so AERS may be filtered using these parameters.
 
PharmaPendium is the only product which provides these possibilities to filter AERS.
 
AERS is updated quarterly by the FDA and PharmaPendium will also update AERS (post-market data) quarterly.

The problem is simple enough, just not (I believe) fixable in the program as it is. When you run an extracted data search (say as an example for monoclonal antibodies with dog studies with liver toxicities) you end up with a nice list of documents (mostly approval package reviews). You then click on a link you want to look at (Pharmacology review for one of the antibodies) and it opens up the PDF of that document. All well and good to that point, but now there is no way to navigate back to the document list (or I haven't figured it out). The best I can manage is to get back to the data search page where I then have to set up the same search all over again.

Workaround:

In order to get search result page user should do the following:

1. Perform Extracted data search
2. Get result page
3. Open PDF document
4. Push Back button twice (as a result user should see home page)
5. Push Forward button (once)

After that user will get search result page.

From Explorer:

Tools -> Internet Options -> Temporary Files; delete the temp files.

The disappearance of the drug list:

Please, make sure that "Do not save encrypted pages to disk" option is unchecked in IE settings. To uncheck this option user should do the following:

1. Open "Tools" menu in IE and pick up "Internet Options" item
2. Go to "Advanced" tab
3. Scroll down to "Security" section (usually it's the last one)
4. Uncheck "Do not save encrypted pages to disk" option

Extracted data search – browsing search results (run an extracted data search, get results, click on a link, no way to navigate back to the document list)

It’s really feature of browser (not application one)

In order to get search result page user should do the following:

1. Perform Extracted data search
2. Get result page
3. Open PDF document
4. Push Back button twice (as a result user should see home page)
5. Push Forward button (once)

After that you should see the search result page.

1. No software is associated with PDF files but Adobe Acrobat is installed. In this case we can suggest the following solutions:

• Set "Display PDF in browser" (Edit -> Preferences -> Internet) checkbox to off, save changes and then enable this option

or

• Reinstall Adobe Acrobat.

Similar issue may occurs if you install both Adobe Reader and Adobe Acrobat, set Adobe Reader as default program to display PDF files and then remove it.

2. PP did not recognise that Adobe Acrobat (v8) was installed

There are 2 variants of such behavior of PharmaPendium:

• You(user) use FireFox browser. Currently PharmaPendium doesn't support FireFox (it doesn't detect Adobe Reader/Acrobat on FireFox).
• Please, make sure that "Display PDF in browser" option is checked in Adobe Acrobat settings. To check this option user should do the following:
• Open "Edit" menu in Adobe Acrobat and pick up "Preferences" item
• Go to Internet tab
• Put a check in the box for the setting and save the change

If this problem is still present, please open Adobe Acrobat before using PharmaPendium. And then, user can use PP without any problems.

For checking if MDL Draw has been installed, you should make sure that c:\Program Files\Java\jre1.5.0_11\lib\ext\" folder contains:

• calculator.jar
• ChimePro.jar
• CsInline.jar
• dbb_client.jar
• dbb_helps.jar
• dbb_images.jar
• editor.jar
• editor_help.jar
• editor_legend.jar
• editor_templates.jar
• extlibs.jar
• mdli_mt.jar

There are no other ways to check if MDL Draw has been installed on your PC.

There is a SCR cct00099020 related to the installation of MDL Draw.

Work around

User should click on "Chemistry Search" again. And chemistry search box will appear.

Yes, contact us at:

Europe, Middle East and Africa

E-Customer Service, Theodor-Heuss-Allee 108, 60486 Frankfurt/Main, Germany, Tel: +49-69-5050 4268, Fax: +49-69-5050 4213, Email: nlinfo@pharmapendium.com

Americas

E-Customer Service, 360 Park Avenue South, New York, NY 10010-1710 USA, Tel: +1 888 615 4500 (+1 212 462 1978, if calling from outside the USA and Canada), Fax: +1 212 462 1974, Email: usinfo@pharmapendium.com

Asia-Pacific

E-Customer Service, 1-9-15 Higashi-Azabu, Minato-ku, Tokyo 106-0044 Japan, Tel: +81 3 5561 5034, Fax: +81 3 5561 5047, Email: jpinfo@pharmapendium.com

All customers are required to have a license with MedDRA, a thesaurus provided by the ICH (MSSO). Most large and medium biopharma account will have this license, however very small biotechs and academics might need to set this up.

On the PharmaPendium interface the following message is displayed:

'The Toxicity / Adverse Effects tree displayed is a combination of terms from RTECS (r), MedDRA (r) and other terms extracted from various content sources. For that reason, this tree cannot be used for coding of human adverse events reports for submission to regulatory agencies. MedDRA(r) should be licensed from the International Conference on Harmonization for that purpose.'

The secure network protocol, HTTPS, is implemented.

PharmaPendium is web-based product. Only when you want to do structure search by importing structure files or drawing your own structure, you need to install MDL Draw onto your computer. Its downloading link is provided with PharmaPendium.

If you only want to search structures from a drug information page, you don’t need to have MDL Draw. You will also need to have Adobe Acrobat Reader 7.0 for optimal use.

Yes.

Java Runtime Environment 1.5 or higher. If the DiscoveryGate installer does not detect this software, it will install this version of the JRE. If the DiscoveryGate installer detects an earlier version of this software, it will install this version as the active version of the JRE. If DiscoveryGate detects a later version of this software, it will not install this version of the JRE. The current version of the JRE will remain the active version. Wee the document DiscoveryGate Installation and Configuration for more information about the JRE.

It is strongly recommended to use Adobe Acrobat Reader 7.0 or better.

ADOBE Reader 7.0 or higher is recommended. Adobe reader 6.0 can be used to read and search the documents, However, there are several known issues with the product using Adobe Acrobat Reader 6.0 that affect the searching efficiency of the FDA Approval Package content source.

• Safari version 2.0.3
• IE version 6.0 SP1