Questions and Answers about the Procedure


Is there an overview of all assessment cases?

The G-BA publishes a special section on early benefit assessment on its website: http://www.g-ba.de/informationen/nutzenbewertung/

There the general public can find information on the current status of all active ingredients in pharmaceuticals for which the G-BA is conducting or has completed early benefit assessments in accordance with the German Social Code, Book Five (SGB V), section 35a. The information is indexed according to the names of active ingredients, not the trade names under which the pharmaceuticals are marketed.

Basic information is published as soon as proceedings start. The benefit assessment is normally published three months after proceedings begin. The dossier is published on the website at the same time as the benefit assessment.

Scope of application

  • What pharmaceuticals are subject to an early benefit assessment in accordance with the German Social Code, Book Five (SGB V), section 35a?

An early benefit assessment in accordance with SGB V, section 35a is performed for all reimbursable pharmaceuticals with new active ingredients or new combinations of active ingredients first marketed after 1 January 2011. If a new indication is authorized for these pharmaceuticals, a benefit assessment in accordance with SGB V, section 35a is performed for this new therapeutic indication as well. No exceptions are permitted for pharmaceuticals used exclusively for inpatients.

If a new indication is authorized for a pharmaceutical marketed before 1 January 2011, no benefit assessment will be conducted in accordance with SGB V, section 35a unless the G-BA had already instigated a benefit assessment in accordance with SGB V, section 35a, paragraph 6.

In general, a dossier must be submitted for all reimbursable pharmaceuticals with new active ingredients according to SGB V, section 35a, paragraph 1. The law explicitly regulates exceptions to this principle in SGB V, section 35a (cf. the regulation in SGB V, section 35a, paragraph 1a on exemptions to the dossier requirement due to negligibility).

  • Under what circumstances are pharmaceuticals exempted from benefit assessment in accordance with SGB V, section 35a?

In some cases a pharmaceutical company can have a pharmaceutical with a new active ingredient exempted from benefit assessment and the dossier requirement (SGB V, section 35a, paragraph 1a in connection with the G-BA rules of procedure (VerfO), chapter 5, section 15, paragraph 1, sentence 3). The requirement for an exemption is that the expected long-term revenue from sales to outpatients charged to statutory health insurance must not exceed 1 million euros within 12 calendar months. In general, the pharmaceutical company must submit a petition to the G-BA in accordance with the G-BA rules of procedure, chapter 5, section 15 if it wants a pharmaceutical to be exempted from benefit assessment in accordance with SGB V, section 35a.

The special case of orphan drugs

  • Are orphan drugs exempt from early assessment?

Orphan drugs are pharmaceuticals for the treatment of rare diseases authorized in accordance with EC regulation number 141/2000 of the European Parliament and Council of 16 December 1999 on orphan drugs. Orphan drugs have a special status in the early benefit assessments of pharmaceuticals with new active ingredients. In accordance with statutory requirements (SGB V, section 35a, paragraph 1, sentence 10) the additional medical benefit of these medications is already proved through market authorization. Proof of medical benefit and additional medical benefit over an appropriate comparator need not be submitted. Only the extent of additional benefit must be proved for the number of patients and patient groups for whom a therapeutically significant additional benefit exists (G-BA rules of procedure, chapter 5, section 12, number 1, sentence 2). In principle, this statutory provision assumes an additional benefit for the orphan drug authorized. It does not require a relevant scientific assessment of the pharmaceutical as a foundation.

Based on this statutory requirement, the G-BA determines the extent of additional benefit for orphan drugs with revenues not exceeding 50 million euros in the past twelve months based on market authorization and its substantiating studies. This limitation on the benefit assessment of orphan drugs resulting from the link to market authorization no longer applies if revenues from the pharmaceutical received through the statutory health insurance at pharmacy retail prices, including VAT, exceed 50 million euros over the past 12 months. In accordance with SGB V, section 35a, paragraph 1, sentence 11, the pharmaceutical company must then send proof in accordance with G-BA rules of procedure, chapter 5, section 5, paragraphs 1 to 6, especially of additional medical benefit over the appropriate comparator determined in accordance with G-BA rules of procedure, chapter 5, section 6, within three months after receiving notification by the G-BA.

  • How does the G-BA monitor whether a manufacturer of an orphan drug achieves an annual revenue of more than 50 million euros or not?

The limit of 50 million euros is based on revenues from the pharmaceutical paid by statutory health insurance at pharmacy retail prices, including VAT, over the past 12 calendar months. Revenues are calculated in accordance with SGB V, section 84, paragraph 5, sentence 4. Regular monitoring is conducted.

  • What dossier documents must pharmaceutical companies submit for an orphan drug with revenues less than 50 million euros?

Module 1
Sections 1.4 (appropriate comparator) and 1.5 (medical benefit and additional benefit) need not be completed.

Module 2
Section 2.2.3 (international market authorization status) need not be completed.

Module 3
Section 3.1 (determination of the appropriate comparator) need not be completed.

Module 4
Only section 4.4.4 must be completed. The details on the extent of additional benefit must be given on the basis of the market authorization and its substantiating studies.

Module 5
The following must be submitted: study reports and study protocols from market authorization studies, all studies submitted to regulatory authorities (cf. G-BA rules of procedure, chapter 5, section 9, paragraph 4, sentence 1) regulatory authority documents (including those of the EPAR), and other documents/complete texts for modules 1-4.

Appropriate comparators

  • What process must be followed when there is no medicinal comparator?

Non-medicinal comparators must also be considered if they are reimbursable by the statutory health insurance (G-BA rules of procedure, chapter 5, section 6, paragraph 3, number 2). These treatments must also belong to the generally recognized medical state of the art for the indication relevant to the application.

  • Doesn't the new pharmaceutical necessarily need to be compared to others from the same class of active ingredients?

The new pharmaceutical is compared to the appropriate comparator considered a standard, according to the generally recognized medical state of the art, for the indication for which the new pharmaceutical was authorized. It can claim an additional benefit and thus a higher price only if it is better than this standard. The standard for an indication need not necessarily be a pharmaceutical from the same class of active ingredients.

For example: the new pharmaceutical is a lipid-lowering drug. If the appropriate comparator is a statin and the new lipid-lowering drug is not, the new pharmaceutical is then compared to a pharmaceutical from a different class of active ingredients.

Compiling dossiers

  • Must the dossier be restricted to studies the company has funded itself, or can it include studies funded by third parties?

The dossier should include all studies, both completed and discontinued, on the relevant active ingredient conducted in whole or in part for the indication relevant to the dossier. These studies may be funded by the company itself or by third parties.

  • The benefit of a new active ingredient can vary according to patient group or indication. How can this be outlined in the dossier?

The dossier template allows various patient groups to be defined within the indication. The extent of additional benefit over the appropriate comparator is to be designated separately for each group. In modules 3 and 4, explicit details are required to show for which patient group(s) a therapeutically significant additional benefit exists.

Patient groups with a therapeutically significant additional benefit can be, for example, patients with a certain severity of disease, disease entity, previous treatment, or a certain age or gender. They can be identified and defined based on the results of medical benefit and additional benefit presented in the dossier.

  • Should the percentage of patients for whom additional benefit can be established be expressed relative to the total number of all patients treated, or to the number of persons affected by this disease?

The number of patients for whom medically significant additional benefit has been determined within the authorized indication must be given. This number must be distinguished from the target population of all patients covered by the authorization. The patient group with therapeutically significant additional benefit can include either the entire target population or a portion thereof.

  • What is the procedure if a pharmaceutical has more than one therapeutic indication? Is the manufacturer required to name several different comparators and patient groups in the dossier?

If a pharmaceutical has more than one therapeutic indication, each indication to be assessed must be coded (A-Z), and the coding recorded in module 2. This code must be used consistently throughout all dossier modules. For each indication, an appropriate comparator and patient group for whom additional medical benefit is proposed must be specified.

  • What is the procedure if there are no precise publications on the number of potential patients?

The best available evidence must be used to determine the number of potential patients. If there is no concrete data on the number of patients, the basis used to calculate the number indicated must be presented.

  • Can additional (sub-)folders be inserted into the structure given for the DVD to be submitted?

The structure described in appendix II - paragraph 4.1 - to chapter 5 of the G-BA rules of procedure contains all directories and sub-directories necessary for the orderly submission of the dossier documents, including all appendices in module 5.

Additional folders or directories are thus not necessary for compiling the dossier, and can cause difficulties in its processing. Therefore no changes should be made to the structure given. Do not insert additional (sub-)directories unless they are explicitly mentioned as necessary, e.g. when considering multiple indications in Modul5_Anlagen/Dateien-fuer-Modul3/Anwendungsgebiet_#A-Z#.

  • Are there other requirements for naming the files?

When naming the files please ensure that the path length for the documents does not exceed 150 characters. It may be necessary to abbreviate the file name.

  • Searchable study registry databases

The information platform clinicalstudyresults.org went offline at the end of 2011.
It is thus no longer possible to search this database.
As in the section "Search in study registries" of appendix II on chapter 5 of the G-BA rules of procedure, the search should include at least the study registries International Clinical Trials Registry Platform (ICTRP) and clinicaltrials.gov.

Documents in module 5 of the dossier

  • Must all study report appendices be submitted?

Study reports must be submitted in their entirety, including all appendices (paragraph 3.1, "Compiling and submitting a dossier on benefit assessment in accordance with SGB V, section 35a"; G-BA rules of procedure, appendix II, chapter 5). Otherwise the study report will not be considered complete. Only appendices that contain patient data listings or other individual, personal details (e.g. information on investigators) need not be included. They can be deleted or rendered illegible. The table of contents for the appendices, with information on all appendices included, must not be deleted or otherwise altered.

  • What published and unpublished documents from the central market authorization proceedings (EMA) must be submitted?

At certain milestones of the proceedings, the EMA compiles various evaluation reports. Of these, the following must be submitted:

  • Rapporteurs’ Day 150 Joint Response Assessment Report
  • Rapporteurs’ Day 180 Joint Response Assessment Report
  • CHMP Assessment Report or European Public Assessment Report (EPAR)

Only those evaluation reports actually compiled for the relevant proceedings, based on the evaluation steps described in the final report, must be included. These do not always include an evaluation report on day 180.

  • How are study reports not written in German or English to be handled?

In accordance with the rules of procedure of the G-BA, all documents included in module 5 of the dossier on early benefit assessment must be submitted in German or English. Study reports in accordance with ICH E3 and their appendices can cover thousands of pages. This would incur considerable translation expense for these special document if they are not written in German or English. Therefore the following simplified rules apply to study reports not written in German or English:

  1. The study report must be submitted in its entirety in the original language (according to the requirements for study reports in German or English).
  2. The following sections must also be submitted in German or English:
  • Core report (corresponding to chapters 1 to 15 in accordance with ICH E3, i.e. including all charts, tables, illustrations, and diagrams referenced but not included in the text (corresponding to chapter 14 in accordance with ICH E3))
  • Study protocol, including all amendments
  • Statistical analysis plan
  • All tables of contents, including tables of contents for the appendices (chapter 16 in accordance with ICH E3)

Submitting dossiers

  • How can the dossier be submitted to the staff office on time? How is this confirmed?

Dossiers must be submitted to the G-BA no later than the times specified in the G-BA rules of procedure, chapter 5, section 8. Those are the governing times the pharmaceutical with a new active ingredient was first marketed and thus included in the "Lauer-Taxe".
If the pharmaceutical has been approved for a new therapeutic indication, the dossier must be submitted within 4 weeks of this authorization.

A confirmation of receipt of a dossier (e.g. delivery by courier) can be issued only during staff office business hours:

Monday – Thursday: 8:00 – 20:00
Friday: 8:00 – 18:00

Outside business hours, the dossier can only be delivered to the G-BA letterbox, but in that case the staff office cannot always confirm punctual delivery, e.g. before midnight on the day of inclusion in the "Lauer-Taxe".
A confirmation of receipt will be sent by post after the dossier has been delivered.

  • What submission deadlines apply to dossiers for market authorization expansions for for pharmaceuticals already on the market?

If a new indication is authorized for a pharmaceutical marketed before 1 January 2011, a benefit assessment will be conducted in accordance with SGB V, section 35a if the G-BA has already instigated a benefit assessment in accordance with SGB V, section 35a, paragraph 6. If the pharmaceutical is authorized for a new indication after instigation but before the start of the benefit assessment procedure for the indication already authorized, the dossier for the new indication must be submitted along with the dossier in accordance with the G-BA rules of procedure, chapter 5, section 16.

If the pharmaceutical is authorized for the new indication during ongoing assessment proceedings for the indication already authorized, the dossier for the new indication must be submitted within 4 weeks after market authorization for the new indication, or of the notification of the pharmaceutical company of approval for a type 2 amendment in accordance with EC regulation number 1234/2008, appendix 2, number 2, letter a. This applies even if the benefit assessment in accordance with the regulation in G-BA rules of procedure, chapter 5, section 16 has not yet been completed.

Hearing procedures

  • File size in email attachments - why am I receiving an error message after sending an email?

Due to technical restrictions, the data volume per email is limited to 20 MB. Larger emails cannot be delivered, and you will receive an error message. If you need to send a larger data volume for a hearing procedure as an email attachment, you can divide it up among several emails. The subject line should then include a clear indication (e.g. part 1, 2,…) of the attachment.

You can always send a hearing statement on an electronic data carrier (CD or DVD) to the G-BA staffed office. In both cases the deadline is based on the date of receipt. Statements received later cannot be considered.

  • Are there any formatting specifications for the submission of a hearing statement?

When submitting hearing statements, please follow appendix III - template for submitting a written statement on benefit assessment in accordance with SGB V, section 35a. All objections must be submitted in the tabular form specified. Extensive text formatting, e.g. format commands for numbered headlines etc., lead to difficulties in processing the statement submitted and should be avoided whenever possible. Endnotes should also be avoided.  

Handling of confidential documents

  • What precautionary measures are in place at the G-BA staff office to ensure that confidential documents submitted do not fall into the wrong hands?

Confidential documents are documents in module 5 of the dossier which the pharmaceutical company has marked as confidential, as well as petitions for exemptions or requests for consultation in their entirety. They must be protected from unauthorized access.

The management of the G-BA staff office has issued a policy for dealing with confidential documents in accordance with SGB V, section 35a, both within the office and in working with advisory committees. This policy is legally binding for all office employees and obliges them to confidentiality. Moreover, all employees who work with confidential documents are obliged to observe the Law on Obligations (http://www.gesetze-im-internet.de/verpflg/BJNR005470974.html).

Agreements on the confidential treatment of documents will be made with the IQWiG and other parties commissioned to perform assessments.

  • How do G-BA committees deal with confidential documents in the advisory process?

Confidential documents are not included in the meeting papers and are not sent to committee members. Instead, information for meetings is prepared and summarized in a manner that does not violate the obligation of confidentiality, but that does include all information relevant to the decision-making process.

  • What precautionary measures can the pharmaceutical company take to support proper handling of confidential documents?

The pharmaceutical company should use two envelopes when submitting dossiers, petitions for exemption, or requests for consultation in accordance with SGB V, section 35a. Please use the G-BA address on the outside envelope. The data carrier with the confidential information, along with a cover letter, should be in a well sealed inside envelope labelled with the notices “Do not open!” and “Dossier submission”, “Request for consultation” or “Petition for exemption”.  For obvious reasons it is not recommended to send documents by normal mail. It is better to send them by courier or registered mail.

  • What documents does the G-BA publish on its website, and what documents are not published?

After completing its consultations on benefit assessments in accordance with SGB V, section 35a, the G-BA publishes its resolutions and the justifications they are based on. The latter include the results of the legally mandated hearing procedure and modules 1 to 4 of the dossier submitted by the pharmaceutical company. All of module 5, as well as decisions on petitions for exemption and documents on requests for consultation, are subject to the obligation of confidentiality and never published on the internet.

Revisability of G-BA decisions

  • Is the result of an early assessment by the G-BA final, or can it be revised based on new findings?

Not earlier than one year after the publication of the resolution on benefit assessment (in accordance with the G-BA rules of procedure, section 20), the pharmaceutical company can request a new benefit assessment if it can demonstrate necessity based new scientific findings (G-BA rules of procedure, chapter 5, section 14). If the G-BA considers this petition justified, it will request the pharmaceutical company to submit a new dossier within 3 months after the decision has been delivered. Apart from this the G-BA can decide, not earlier than one year after a resolution on benefit assessment, that a new benefit assessment should be performed due to new scientific findings (G-BA rules of procedure, chapter 5, section 13). Resolutions can also be subject to a time limit.

Price negotiations with statutory health insurance providers

  • Once a price has been negotiated between a manufacturer and the Central Federal Association of Health Insurance Funds, does it remain fixed forever, or can it be revised?

Price negotiations between the manufacturer and the Central Federal Association of Health Insurance Funds are not primarily the responsibility of the G-BA.

For example, new price negotiations are possible if there are new scientific findings after a new benefit assessment (G-BA rules of procedure, sections 13 or 14).