This is the text extract for Guidelines for Suppliers’ Submissions, browse documents here.

---

GUIDELINES FOR SUBMISSIONS TO PHARMAC AND PTAC ON NEW CHEMICAL ENTITIES AND GENERIC PHARMACEUTICALS

2005

(amended December 2006)

A97845 -

---

Section A:

Requirements for Submissions for New Chemical Entity Pharmaceuticals 3 1 Introduction..................................................................................................... 3 2 General Matters Concerning Applications....................................................... 3 2.1 Balanced Information............................................................................... 3 2.2 Estimates and Assumptions..................................................................... 3 2.3 Recommended Methods to Derive Clinical Inputs.................................... 3 2.4 Confidentiality .......................................................................................... 4 2.5 Incomplete Applications........................................................................... 4 3 Format and Content of Applications................................................................ 4 3.1 Synopsis.................................................................................................. 4 3.2 Information required in an application ...................................................... 4 3.2 (A) Pharmacological Information................................................................ 4 3.2 (B) Therapeutic Information ....................................................................... 5 3.2 (C) Price Information .................................................................................. 5 3.2 (D) Epidemiological Information ................................................................. 5 3.2 (E) Market Information ............................................................................... 6 3.2 (F) Costs and Benefits ............................................................................... 6 3.2 (G) Decision Criteria Assessment............................................................... 7 3.2 (H) Supporting Literature............................................................................ 9 3.2 (I) Gazette Notice ................................................................................... 10 3.2 (J) Data Sheet ......................................................................................... 10 3.2 (K) Sample............................................................................................... 10 3.2 (L) MAAC Response................................................................................ 10 Section B: Requirements for Submissions for Generic Pharmaceuticals ............. 11 1 Introduction................................................................................................... 11 2 General Matters Concerning Applications..................................................... 11 2.1 Balanced Information............................................................................. 11 2.2 Estimates and Assumptions................................................................... 11 2.3 Confidentiality ........................................................................................ 11 2.4 Incomplete Applications......................................................................... 11 3 Format and Content of Applications.............................................................. 11 3.1 Synopsis................................................................................................ 11 3.2 Other Required Information ................................................................... 12 3.2 (A) Pharmacological Information.............................................................. 12 3.2 (B) Therapeutic Information ..................................................................... 12 3.2 (C) Price Information ................................................................................ 12 3.2 (D) Market Information ............................................................................. 12 3.2 (E) Patents............................................................................................... 12 3.2 (F) Gazette Notice ................................................................................... 13 3.2 (G) Data Sheet ......................................................................................... 13 3.2 (H) Sample............................................................................................... 13

A97845 -

---

Section A: Submissions for Pharmaceuticals

New

Chemical

Entity

1

Introduction

This document sets out the information to be submitted in any application for an addition or amendment to the Pharmaceutical Schedule. Applications and supporting information should be sent to: Chief Executive PHARMAC Level 14 Cigna House 40 Mercer Street PO Box 10-254 WELLINGTON 6001 Attention: Therapeutic Group Assistant These guidelines are subject to the policies and procedures set out in PHARMAC’s Operating Policies and Procedures (“OPPs”) (which are available on line at http://www.pharmac.govt.nz/download/OPPs.pdf), including those in section 4 of the OPPs.

General Matters

2.1 Balanced Information The submission must include all relevant information known to the applicants including data that is contrary to or does not necessarily support their case. 2.2 Estimates and Assumptions In all cases where estimates and assumptions are made, these should be clearly and explicitly stated and include the underlying reasons for making them and their source. Estimates and assumptions may be indicated in ranges. 2.3 Recommended Methods to Derive Clinical Inputs Details of desirable clinical information to supplement the information asked for in section 3.2 (B) ‘Therapeutic Information’ below, can be found in PHARMAC’s ‘Recommended Methods to Derive Clinical Inputs for Proposals to PHARMAC’ (on-line at http://pharmac/pdf/62465.pdf). Some of the information requested is an ideal, and may not be relevant or necessary for every application. As a general guide, greater clinical and epidemiological detail is needed for pharmaceuticals with major potential impacts on total costs and/or population health gains compared with those having a smaller impact.

A97845 -

---

2.4 Confidentiality The confidentiality of applicants’ submissions is addressed in clause 4.3 of the OPPs. 2.5 Incomplete Applications If an application is incomplete in any way, or if clarification is required, PHARMAC may contact the applicant and may have to defer consideration by PTAC until the applicant has resolved any outstanding issues.

3

Format and Content

The synopsis, application and supporting information should be provided in spiral bound volumes with the date of the application on the front cover. Applicants should also supply one electronic copy of the submission on Compact Disk with three documents – synopsis, application and references/literature. 3.1 Synopsis Applicants must provide fifteen copies of a brief synopsis (we recommend ten pages or less) of all material issues referred to in the application and supporting information. The synopsis will be used as a general information guide for PHARMAC staff and will be included in the PTAC meeting agenda papers. Copies of the synopsis must be provided separately from the rest of the application. 3.2 Full Application Applicants must provide fifteen copies, containing the following information (in the order set out below). Where any information is not available or is otherwise not supplied, please state so explicitly under the relevant heading(s). 3.2 (A) Pharmacological Information Please provide the following information: (i) (ii) official or approved names of the pharmaceutical; forms, strengths and arranged pack sizes: In the case of a preparation such as an aerosol, state the number of doses available from the container; (iii) (iv) (v) principal pharmacological action of the pharmaceutical; registered indications, other indications; recommended dosages for each of the indications provided in connection with (iv) above: In the case of a pharmaceutical that is not used for chronic therapy, provide information on the average length of a treatment course and anticipated frequency of repeat courses of treatment; (vi) any contra-indications, interactions and adverse effects:

A97845 -

---

Include information on any necessary dosage adjustments and cautions required when using the pharmaceutical in conjunction with other pharmaceuticals. 3.2 (B) Therapeutic Information Please provide the following information: (i) (ii) (iii) the therapeutic group and/or sub-group into which the applicant considers the pharmaceutical should be listed on the Pharmaceutical schedule; summary statement of the main therapeutic claims for the pharmaceutical and its proposed use; how the pharmaceutical compares clinically with pharmaceuticals already listed on the Pharmaceutical Schedule, including: · what (if any) advantages the pharmaceutical offers over existing pharmaceuticals in terms of efficacy and/or side effects:

q

whether the pharmaceutical pharmaceuticals;

is

equivalent

to

existing

q

whether the pharmaceutical is more effective than existing pharmaceuticals; whether the pharmaceutical has a similar efficacy to existing pharmaceuticals but has fewer side effects;

q

·

whether the pharmaceutical is associated with similar, greater or fewer side effects and/or toxicity than existing pharmaceuticals;

For further details of desirable supplementary clinical information, and in what order to place any such information, see section 2.3 above and ‘Recommended Methods to Derive Clinical Inputs for Proposals to PHARMAC’ (on-line at http://pharmac/pdf/62465.pdf) whether the pharmaceutical offers greater convenience (e.g., once daily dosing) than existing pharmaceuticals; (iv) (v) whether the pharmaceutical pharmaceuticals; and has a longer shelf-life than existing

other pharmaceuticals, medical devices, related products or things, if any, likely to be prescribed for use in conjunction with the pharmaceutical as part of a course of treatment. Include pharmaceuticals that may be used to manage any side-effects.

3.2 (C) Price Information Please provide the following information: (i) (ii) the supplier’s selling price in $NZ (ex-manufacturer, GST exclusive); the supplier’s selling prices to wholesalers in other countries where the pharmaceutical is marketed (in local currencies (excluding local taxes) and New Zealand dollar equivalents – please note the exchange rates used); alternative pricing proposals (e.g., possible price/volume trade-offs).

(iii)

A97845 -

---

3.2 (D) Epidemiological Information For each recommended indication, please provide estimates for the first five years of listing (shown on a year-by-year basis) of the numbers of: (i) (ii) (iii) (iv) (v) people in New Zealand with the particular condition(s); where available, Maori people in New Zealand with the particular condition(s); where available, Pacific peoples in New Zealand with the particular condition(s); people in New Zealand likely to seek treatment for the condition(s); and/or people in New Zealand likely to be prescribed the pharmaceutical; a breakdown of people in New Zealand treated for the condition by: · · · · those who can be successfully treated by the pharmaceutical only; those who can be treated by both the pharmaceutical and other pharmaceuticals that treat the same condition; those who can be treated by only other pharmaceuticals; and those who can be treated, completely or partially, by other therapies.

Further details of desirable epidemiological information can be found in the two sections ‘Epidemiology, Public Health Significance and Estimated Utilisation’ and ‘Need by Maori and Pacific peoples’ of PHARMAC’s ‘Recommended Methods to Derive Clinical Inputs for Proposals to PHARMAC’ (on-line at http://pharmac/pdf/62465.pdf). In all cases where estimates and assumptions are made or used, please clearly and explicitly state the bases underlying those estimates and assumptions, including sources. Estimates and assumptions may be indicated in ranges. 3.2 (E) Market Information Please provide the following information: (i) estimated average daily dose (ADD) information for New Zealand (and other markets where possible) and estimated average daily cost (ADC) of treatment for New Zealand; expected sales (dollars and volume) for the first five years of listing, to be shown on a year-by-year basis with anticipated market segments and projected market shares; and what marketing will be used for the pharmaceutical and how this will relate to market penetration.

(ii)

(iii)

The ADD, ADC and expected sales information referred to in (i) and (ii) above should be supported by data from major OECD markets and other markets where the pharmaceutical is available (i.e. therapeutic indication(s) and use, ADD information, ADC of treatment, and sales). These data should cover the time period from product launch within each market to the date of the application, on a year-by-year basis.

A97845 -

---

3.2 (F) Costs and Benefits Where available, please provide information on the costs and benefits to individual patients of listing or widening access to the pharmaceutical. This must include the direct monetary costs to DHBs of subsidising the pharmaceutical. It may include monetary costs and benefits, such as reductions in expenditure in other health services as a result of listing the pharmaceutical. It may also include other quantitative or qualitative, monetary or non-monetary costs and benefits. Economic principles used by PHARMAC include: · · · · using costs to the Pharmaceutical Schedule, other health sector (Vote: Health) costs and direct patient costs when measuring effects on overall costs; measuring gains in quality-adjusted life expectancy (QALY gains); discounting both costs and QALY gains according to PHARMAC’s current rate [8%]; and uni/multivariate sensitivity analyses.

Include these aspects in any economic analyses submitted to PHARMAC, along with the detail of their clinical assumptions as described by PHARMAC’s ‘Recommended Methods to Derive Clinical Inputs for Proposals to PHARMAC’. Further details on cost and benefits information can be found in PHARMAC’s ‘Prescription for Pharmacoeconomics’ (on-line at http://www.pharmac.govt.nz/download/pfpa.pdf) and PHARMAC’s ‘Recommended Methods to Derive Clinical Inputs for Proposals to PHARMAC’ (on-line at http://pharmac/pdf/62465.pdf). 3.2 (G) Decision Criteria Assessment Please provide evaluation of the proposal against as many as possible of PHARMAC’s nine decision criteria, described below.

Some important contextual notes about the decision criteria and questions listed beneath them When making decisions on proposals, PHARMAC uses the decision criteria set out below and gives such weight to each criterion as it considers appropriate. These decision criteria are set out in section 2.2 of PHARMAC’s OPPs. The criteria are also used by PTAC when it assesses applications. Below, under each of the listed criteria, is a series of questions. The questions have been included to help applicants to address each criterion. PHARMAC has also identified some potentially relevant supporting information, which it would, where available, be helpful for applicants to provide in relation to each criterion. The questions and supporting information identified below do not limit either the application of each criterion or the factors PHARMAC may consider under each criterion.

A97845 -

---

The decision criteria are: (i) The health needs of all eligible people within New Zealand; What health need(s) does this proposal meet? Where available, include estimates of 1. population disability-adjusted life years (DALY) lost for the disease(s); 2. the disease’s % of population total DALY loss across all diseases (543,000 DALYs lost in 1996); and 3. the extent (%) to which the disease(s) are modifiable by the proposal. (ii) The particular health needs of Maori and of Pacific peoples; What particular health need(s) of Maori and of Pacific peoples does this proposal meet? Where available, include estimates of excess DALY loss for Maori and for Pacific people when compared with others (suggesting potential for health gain) (iii) The availability and suitability of existing medicines, therapeutic medical devices and related products and related things; What other interventions are currently available to meet these health needs – if there are none, what other health sector resources are used managing the need(s)? (iv) The clinical benefits and risks of pharmaceuticals; What health benefits and risks does the proposal provide, including in comparison with the other interventions outlined above? Where available, include estimates of 1. absolute risk reductions (ARR) in events (specify) or improvement in health states (specify) caused by the proposal; and 2. discounted QALY gains per patient treated over one year. (v) The cost-effectiveness of meeting health needs by funding pharmaceuticals rather than using other publicly funded health and disability support services; What is the incremental cost (or saving) and incremental benefit (or risk) compared with the other interventions? Where available, include 1. estimate of incremental cost-utility ratio (IUCR) in $/QALYs; and 2. justification of the price (i.e. an estimate of the adjusted price per patient per year required to achieve an ICUR of a notional $10,000/QALY). (vi) The budgetary impact (in terms of the pharmaceutical budget and the Government’s overall health budget) of any changes to the Pharmaceutical Schedule;

A97845 -

---

What impact does this proposal have on the pharmaceutical budget and the overall health budget, both for the current financial year and the net present value (NPV) of the effects over future years? (vii) The direct cost to health service users; How are patients’ out-of-pocket expenses changed by the proposal? (viii) The Government’s priorities for health funding, as set out in any objectives notified by the Crown to PHARMAC, or in PHARMAC’s Funding Agreement, or elsewhere; and Such other criteria as PHARMAC thinks fit. PHARMAC will carry out appropriate consultation when it intends to take any such “other criteria” into account.

(ix)

Note that PHARMAC is not bound to accept the applicant’s evaluation of the application against the decision criteria, and may attribute different weightings to criterion. 3.2 (H) Supporting Literature Please provide a copy of your search strategy. Where possible provide copies of articles published in peer-reviewed international medical literature. All articles submitted should be written in English or accompanied by a certified English translation. Information provided should relate only to the pharmaceutical and disease(s)/indications under consideration. Unrelated or irrelevant articles will not be reviewed. Copies of unpublished articles or studies that have been submitted for peer review will also be accepted for consideration. If the published article becomes available after the application has been submitted, applicants may substitute the draft with the final version. Do not submit copies of any case histories or clinical correspondence relating to individual patients. Where possible, critically appraise and grade the articles using the methods described in PHARMAC’s ‘Recommended Methods to Derive Clinical Inputs for Proposals to PHARMAC’ (on-line at http://pharmac/pdf/62465.pdf). Subdivide the copies of the articles, with their accompanying appraisals and gradings (where applicable), into each of the following three categories: (i) (ii) published Grade 1 evidence of effectiveness, i.e. randomised controlled trials (RCTs) of efficacy (individual RCTs and meta-analyses of RCTs); published Grade 2-3 evidence of effectiveness, i.e. controlled but nonrandomised experimental studies and non-analytic uncontrolled descriptive data for efficacy (prospective cohort studies, case control studies, beforeand-after studies longitudinal studies, uncontrolled observational studies, case reports); and

A97845 -

---

(iii)

published Grade 4 evidence of effectiveness PLUS all other published material, i.e. non-systematic reviews, expert opinion, economic modelling/analyses in absence of direct empirical data, background epidemiology and natural history of the disease/indication, and other published material relevant to the proposal.

Within each group, please order articles by date of publication. 3.2 (I) Gazette Notice Include a copy of the gazette notice or the notice to distribute a changed medicine. 3.2 (J) Data Sheet Include a copy of the approved data sheet. 3.2 (K) Sample Provide one labelled sample of the pharmaceutical, as appropriate. More samples may be required. 3.2 (L) MAAC Response Include a copy of New Zealand Medicines Assessment Advisory Committee (MAAC) response to registration application.

A97845 -

---

Section B: Guidelines for Submissions to PHARMAC/ PTAC on Generic Pharmaceuticals

1

Introduction

This document sets out the information to be submitted in any application made by suppliers for an addition or amendment to the Pharmaceutical Schedule with respect to generic pharmaceuticals. Applications and supporting information should be sent to: Chief Executive PHARMAC Level 14 Cigna House 40 Mercer Street PO Box 10-254 Wellington 6001 Attention: Therapeutic Group Assistant

2

General Matters

2.1 Balanced Information The submission must include all relevant information known to applicants, including data that is contrary to or does not necessarily support their case. 2.2 Estimates and Assumptions In all cases where estimates and assumptions are made, these should be clearly and explicitly stated and include the underlying reasons for making them and their source.. Estimates and assumptions may be indicated in ranges. 2.3 Confidentiality The confidentiality of applicants’ submissions is addressed in Clause 4 of PHARMAC’s Operating Policies and Procedures (OPPs) (on line at http://www.pharmac.govt.nz/download/OPPs.pdf). 2.4 Incomplete Applications If an application is incomplete in any way, or if clarification is required, PHARMAC may contact the applicant and may have to defer consideration by PTAC until the applicant has resolved any outstanding issues.

3

Format and Content of Applications

3.1 Synopsis Applicants must provide fourteen copies of a brief synopsis of all material issues referred to in the application and supporting information. . The synopsis and

A97845 -

---

supporting information should be provided in a soft cover folder, with two holes punched, and the date of application on the front cover. An electronic copy of the submission either on Compact Disk or Diskette is also useful. Copies of the synopsis must be provided separately from the supporting information. If it is decided that the application needs to be discussed at PTAC, then a further ten copies of the synopsis, and supporting information will be required. 3.2 Other Required Information

Registration Status Supporting the application should be four copies of the following information (in the order set out below): 3.2 (A) Pharmacological Information Pharmacological information about: (i) (ii) official or approved names of the pharmaceutical; forms, strengths and arranged pack sizes: In the case of a preparation such as an aerosol, the number of doses available from the container should be stated; (iii) (iv) expected date of MedSafe registration and indication if being fast-tracked; and approved indications.

3.2 (B) Therapeutic Information Therapeutic information about: (i) (ii) (iii) (iv) (v) the IMM status of the generic; the efficacy of the generic compared with existing pharmaceuticals and the side effect and toxicity profile of the generic; its bioequivalence study; whether the pharmaceutical has a longer shelf-life than brands currently listed; and any differences between generic and other brands currently listed.

3.2 (C) Price Information Price information about: (i) (ii) the supplier’s selling price (GST exclusive); and alternative pricing proposals (e.g., possible price/volume trade-offs).

3.2 (D) Market Information Estimated size of market and expected uptake. 3.2 (E) Patents Any patent investigation carried out by the supplier

A97845 -

---

3.2 (F) Gazette Notice A copy of the gazette notice or the notice to distribute a changed medicine. 3.2 (G) Data Sheet A copy of the approved data sheet. 3.2 (H) Sample One labelled sample of the pharmaceutical, as appropriate. More samples may be required.

A97845 -