XVI.Add.III.3. Risk minimisation measures constituting a PPP

A pregnancy prevention programme (PPP) is a set of routine and additional risk minimisation 97 measures (RMM). In principle, a PPP should include all the following pregnancy-specific RMM, which need to fulfil the requirements described in GVP Module XVI:

• Summary of product characteristics (SmPC) and package leaflet (PL) with the following:
  • Contraindication in pregnancy;
  • Contraindication in women of childbearing potential who are not applying effective contraceptive measures; and
  • Information on the teratogenic risks of the product and related recommendations in the sections on warnings (i.e. SmPC section 4.4 and PL section 2) and on pregnancy (i.e. SmPC section 4.6 and PL section 2), which may also include criteria defining women who are not of childbearing potential5 (see CHMP Guideline on Risk Assessment of Medicinal Products on Human Reproduction and Lactation: from Data to Labelling6);
• Required conditions of prescribing (as also defined in the SmPC and PL and referred to in educational materials) including the following:
  • Before treatment start:
    • Assessment of the patient’s potential for becoming pregnant and for following the PPP; and
    • Personal counselling session of the patient by a healthcare professional on:
      • teratogenic risks of the product;
      • need to avoid pregnancy while using the product and to apply effective contraceptive measures;
      • importance of discussing with a healthcare professional if the wish for conceiving a child exists; and
      • time after treatment discontinuation during which pregnancy will also need to be avoided (where the active substance and/or its metabolites (if teratogenic) have a long half-life; usually this would be five times the half122 life of the active substance)
  • At treatment start:
    • Confirmation of absence of pregnancy through a recent negative pregnancy test, unless one criterion for considering that the woman is not of childbearing potential is met (see Footnote 6); and
    • Counselling on effective contraceptive measures
  • During treatment:
    • Confirmation of absence of pregnancy at an appropriate frequency, normally through a negative pregnancy test, unless one criterion for considering that the woman is not of childbearing potential (see Footnote 6) is met; and
    • Reminder personal counselling sessions on:
      • need to avoid pregnancy while using the product and to apply effective contraceptive measures;
      • importance of discussing with a healthcare professional if the wish for conceiving a child emerges; and
      • the reasons why counselling sessions are needed with the frequency considered appropriate given the context of product use
  • At treatment end, taking into account the half-life of the active substance and its teratogenic metabolites:
    • Confirmation of absence of pregnancy at an appropriate frequency, normally through a negative pregnancy test, unless one criterion for considering that the woman is not of childbearing potential (see Footnote 6) is met; and
    • Reminder personal counselling session on:
      • time period during which pregnancy will also need to be avoided
• Required conditions of dispensing (as also defined in the SmPC and PL and referred to in educational materials), e.g.:
  • Dispensing within a limited number of days after the prescription date;
  • Dispensing a limited quantity of product to ensure that treatment start is aligned with a negative pregnancy test (how this is achieved can differ between Member States);
  • Accessibility to the dispenser of the confirmation that the patient has been counselled regarding the teratogenic risks and understands the need to avoid product use during pregnancy in line with the recommendations from competent authorities in Member States;
  • No allowance for free samples of the product;
• Educational materials targeting healthcare professionals (e.g. in guides, checklists or other materials as applicable, see GVP Module XVI) which includes key information on the following:
  • Teratogenic risks of the product;
  • Required pregnancy testing, the required conditions of prescribing and dispensing and the required personal counselling of the patient;
  • Need to ensure that effective contraceptive measures are applied; and
  • Guidance on how to act in the case of pregnancy and how to help ensure that any possible pregnancy outcomes are evaluated appropriately;
• Educational materials targeting patients which includes key information on the following:
  • Teratogenic risks of the product;
  • Required actions to avoid use of the product during pregnancy, e.g. applying effective contraceptive measures;
  • Need for a negative pregnancy test result to be verified by a healthcare professional before treatment start and be repeated at suitable intervals during and after treatment if applicable;
  • Guidance on the need to consult a healthcare professional in the case of pregnancy;
  • Counselling before treatment start and regularly during and after treatment, and also in the event of a pregnancy (with evaluation of the outcome of any pregnancy); and
  • Handling of any unused product in line with Member States and local procedures to avoid misuse and accidental exposure (including advice to return unused medicine at the end of treatment to the physician or pharmacist)

The abovementioned items can be conveyed by the use of RMM tools such as guides, patient cards or risk awareness forms (see GVP Module XVI), in particular:

• • • Patient card with key messages acting as a reminder of:
      • teratogenic risks of the product;
      • need to avoid use of the product during pregnancy; and
      • associated PPP requirements

Where there are other important identified risks with the product to be displayed on a patient card, the information on teratogenicity must be clearly visible; only in very exceptional circumstances may it be necessary to have a separate patient card on teratogenicity.

• • • Risk awareness form for each patient to confirm the patient has been fully informed of the teratogenic risk of the product and understands the need to avoid product use during pregnancy. The format of such a risk awareness form, e.g. electronic in addition to paper based materials or recording in the patient’s medical record, will depend on what is 192 most suitable given the context of product use and the applicable legal framework of each Member State.

Further, when requiring a PPP, the following pregnancy-specific RMM should be considered to become part of the PPP:

• Labelling of the outer packaging that includes an explicit statement in words on the need to avoid pregnancy when using the product (e.g. “CAN SERIOUSLY HARM AN UNBORN BABY. Women must use effective contraception. Do not use if you are pregnant or think you may be pregnant.”) via a visual reminder such as a boxed warning or a pictogram (the details of the visual reminder should be agreed at Member States’ level and be subject to a user test taking 201 into account input from local patient representatives);
• As needed, a direct healthcare professional communication (DHPC) (see GVP Module XV) about the PPP can become part of a PPP if a new active substance, new population, or a newly identified teratogenic risk is concerned.

On a case-by-case basis, considering relevant aspects of the risk/safety profile and the treatment setting of the medicinal product, a controlled access programme in line with GVP Module XVI, may be required in addition to a PPP. Because of differences between healthcare systems in Member States, some of the routine and 209 additional RMM listed above may need to be implemented in different ways in Member States.